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Mitochondrial dysfunction in Parkinson’s disease – a key disease hallmark with therapeutic potential

Martin T. Henrich, Wolfgang H. Oertel, D. James Surmeier and 1 more (opens in a new tab)

Molecular Neurodegeneration · 2023 · Review · CC BY

doi:10.1186/s13024-023-00676-7 (opens in a new tab)

Abstract

Mitochondrial dysfunction is strongly implicated in the etiology of idiopathic and genetic Parkinson’s disease (PD). However, strategies aimed at ameliorating mitochondrial dysfunction, including antioxidants, antidiabetic drugs, and iron chelators, have failed in disease-modification clinical trials. In this review, we summarize the cellular determinants of mitochondrial dysfunction, including impairment of electron transport chain complex 1, increased oxidative stress, disturbed mitochondrial quality control mechanisms, and cellular bioenergetic deficiency. In addition, we outline mitochondrial pathways to neurodegeneration in the current context of PD pathogenesis, and review past and current treatment strategies in an attempt to better understand why translational efforts thus far have been unsuccessful.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 22, 2026. Paragraph numbers are ours, so an answer can point at one.

Background

1Parkinson’s disease (PD) is the most prevalent neurodegenerative movement disorder affecting up to 2 % of those aged 60 years and older. Clinically, PD is defined by presence of the levodopa-responsive motor symptoms bradykinesia with resting tremor or rigidity. These motor symptoms are frequently accompanied by non-motor symptoms, including but not limited to sleep disturbances, depression, autonomic dysfunction, and hyposmia. Today, there are still no proven strategies for slowing the progression of PD. This unmet medical need reflects our incomplete grasp of disease mechanisms.

2Neuropathologically, PD is characterized by two imperfectly aligned features: selective neuronal degeneration of vulnerable cell-types within particular brain regions (e.g., midbrain dopaminergic (DA) substantia nigra pars compacta (SNc) neurons), and the presence of eosinophilic alpha-synuclein (aSYN) positive inclusion bodies, termed Lewy pathology (LP). Systematic cross-sectional characterization of human postmortem PD brains revealed that even in late-stage disease LP is not globally distributed in the brain of PD patients, but is restricted to certain vulnerable nuclei, thereby showing a patch-like distribution. While there is clear evidence that some regions (SNc, olfactory bulb, dorsal motor nucleus of vagus, locus coeruleus, pedunculopontine nucleus, amygdala) are more susceptible to LP than others, it has been difficult to establish the sequence and extent in which they develop LP. In addition to brain pathology, LP also affects many structures of the peripheral nervous system (nerve fibers within e.g., skin, heart, esophagus). The observation that misfolded, fibrillar forms of aSYN can propagate from one cell to another in PD animal models, has fueled the thought that also in humans toxic aSYN species might spread between synaptically coupled brain regions, thereby driving the development of brain-wide LP formation.

3In contrast to the relatively well-mapped distribution of LP, the spatio-temporal development of cell-loss within affected regions remains largely elusive. While loss of dopaminergic SNc neurons has been well-documented and clearly linked to the onset of PD motor symptomatology, there is no brain-wide assessment of neurodegeneration, and the available studies investigating cell loss show notable heterogeneity. Given the absence of a clear correlation between LP formation and neuronal cell loss, it is crucial to disentangle the cell-intrinsic factors which render neurons susceptible to LP formation and those who drive neurodegeneration. So far, several core pathogenetic factors have been identified. Among those are impaired cellular protein homeostasis, dysfunctional proteasomal and lysosomal clearance systems, impaired protein and membrane trafficking, synaptic dysfunction including disturbed neurotransmission, neuroinflammation, and mitochondrial dysfunction.

4Mitochondrial dysfunction has long been implicated as a key pathological hallmark in PD. Since mitochondria are highly multifunctional organelles, their integrity is essential for neuronal function and survival. This review summarizes the evidence for mitochondrial dysfunction in genetic and idiopathic PD, discusses the bidirectional interaction between mitochondrial stress and aSYN aggregation, and points out potential mitochondrial pathways to neurodegeneration in the current context of PD pathogenesis. Further, we review current and past therapeutic strategies targeting mitochondrial dysfunction in an attempt to modify disease progression, and outline current gaps in our understanding.

Importance of mitochondrial health in PD at-risk neurons

5Neurons possess a complex network of mitochondria stretching from dendrites that receive synaptic contacts to the synaptic terminals that communicate with neighboring neurons. Mitochondria perform a variety of tasks, including generation of adenosine triphosphate (ATP), Ca2+ buffering and epigenetic signaling. Two central tenets of the mitochondrial theory of pathogenesis are that neurons have a high bioenergetic demand and that neurons rely heavily on mitochondria for ATP production. Indeed, all cells rely upon ATP to drive basic cellular processes. Neurons differ from many other cell types in ways that increase their bioenergetic needs. In particular, they need ATP to maintain ionic homeostasis which is being constantly challenged by 1) their reliance upon electrical signals generated by transmembrane ion fluxes, 2) their sequestration of transmitter into vesicles, fusion of these vesicles during synaptic activity and reuptake of membrane during vesicular recycling, and 3) the need to maintain and repair an often massive transmitter release machinery. The ATP necessary for these processes can be derived both from glycolysis and mitochondrial oxidative phosphorylation (OXPHOS). While glycolytic mechanisms are fast, they are relatively inefficient and generate roughly one tenth the ATP from glucose that mitochondria can extract. It has been hypothesized that neurons rely exclusively upon mitochondrial OXPHOS for ATP generation (using lactate shuttled from astrocytes), but more recent direct measurements have shown that neurons use both glycolysis and OXPHOS to generate ATP.

6Despite the clear importance of mitochondria to neuronal bioenergetics, they also play a variety of other roles. One of these is Ca2+ buffering. This may be particularly important in axons of some neurons. Another important function is metabolic signaling. For example, mitochondria are critical sources of citrate, which is important to the production of acetyl-coenzyme A and acetylation of proteins and DNA.

7Compromised mitochondrial function may have a disproportionate impact on those neurons that are at-risk in PD. The best studied example of this phenotype is the SNc dopaminergic neuron. These neurons are constantly active and have extensive axonal arbors with as many as 1–2 million transmitter release sites per axon in humans. Many (if not all) of the other neurons at greatest risk in PD have a similar phenotype: locus coeruleus noradrenergic neurons, dorsal motor nucleus of the vagus cholinergic neurons, and pedunculopontine nucleus cholinergic neurons. These neurons play a key role in organismal survival, particularly during times of crisis when sustained, efficient function is critical.

8To meet this bioenergetic demand, many at-risk neurons engage a feed-forward control mechanism that utilizes plasma membrane L-type Ca2+ channels to drive mitochondrial OXPHOS. While this feed-forward control helps to ensure that ATP levels do not fall during times of high demand, it also increases the production of damaging reactive oxygen species (ROS) and basal mitochondrial oxidant stress. ROS and mitochondrial oxidant stress damages lipids, proteins and DNA. This can not only compromise cellular function but leads to an increased demand on catabolic processes in neurons, most importantly lysosomal degradation. This increased demand should in principle decrease spare capacity, providing a linkage between mitochondrial stress and genetic mutations linked to familial cases of PD involving mitochondrial quality control (DJ1, PINK1, parkin) and lysosomal function (GBA1, LRRK2, VPS35, others).

Evidence for mitochondrial impairment in PD patients

9A key piece of evidence that mitochondrial dysfunction is implicated in PD pathogenesis stems from the observation in 1983 that several recreational drug users which intravenously administered the new synthetic heroin drug MPPP (1-methyl-4-phenyl-4-propionoxy-piperidine) developed acute-onset but levodopa (L-DOPA) responsive parkinsonian motor symptoms shortly after drug administration. Subsequently, the mitochondrial ETC inhibitor MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) was identified as a byproduct of poor MPPP synthesis. Following absorption, MPTP crosses the blood-brain barrier and is converted to MPP+ within astroglia by monoaminoxidase B (Fig. 1). Extracellularly released MPP+ is then actively taken up via the DA transporter and accumulates within mitochondria of DA neurons where it inhibits mitochondrial complex I (CI) of the ETC. Since its first discovery, MPTP induced toxicity has been established and validated many times as a reliable approach to model neurodegeneration and development of motor symptoms in rodents and primates. From a translational standpoint, the MPTP studies have taught us that mitochondrial CI inhibition in DA SNc neurons can cause a disease phenotype that resembles many features of idiopathic PD, e.g. all cardinal motor symptoms (bradykinesia, rigidity, tremor), some non-motor symptoms (dribbling of saliva, urinary disturbances), and L-DOPA responsiveness.

10The observation that CI blockade can induce PD-like symptoms is further substantiated by the finding that the chemically related substance paraquat, as well as the CI inhibitor rotenone (Fig. 1), are not only shown by epidemiology to be risk factors for the development of PD, but also induce PD-like symptomatology in animal experiments. More recently, genetic approaches have shown that disruption of CI function specifically in dopaminergic neurons is sufficient to produce a progressive, L-DOPA-responsive parkinsonism.

11But is mitochondrial dysfunction also a constant and reliable feature of idiopathic PD, meaning in the absence of mitochondrial toxins or genetic disease drivers? Important aspects can be derived from the analyses of brain tissue from deceased idiopathic PD patients. In several studies, tissue samples of the SNc but also of other brain regions, as well as lymphocytes and platelets were analyzed for the presence of ETC alterations by immunoblotting, immunohistochemistry, or enzyme activity analysis. The most pronounced and consistently reported finding is a decreased activity of CI of the ETC in SNc tissue homogenates. Some studies even observed a decreased activity of CI in tissue samples from the frontal as well as prefrontal cortices and striatum, but not peripheral tissues. In contrast, deficiency of ETC CII, CIII or CIV was only sporadically observed, and when ETC function was either assessed by immunohistochemistry or other peripheral specimens (e.g. lymphocytes, platelets, or muscle) were analyzed, CI dysfunction was only inconsistently reported.

12Regarding the lack of concordance in some studies it is important to consider that most experiments either used mixed tissue homogenates (neuronal and non-neuronal cells), or investigated peripheral tissue, which from our current point of view is likely not the main manifestation place of PD pathology. Future studies investigating ETC dysfunction in human postmortem tissue using now available cell-type specific approaches might therefore possess great potential to further enhance our understanding of mitochondrial dysfunction in idiopathic PD.

13Another line of evidence pointing to mitochondrial dysfunction in PD is based on the observation of increased mitochondrial DNA (mtDNA) aberrations in tissue samples of deceased patients with idiopathic PD. While initial approaches investigating mtDNA deletions produced conflicting results, more recent studies confirmed an increased amount of mtDNA deletions specifically in postmortem SNc tissue of PD patients. In addition, patients carrying a mutation of the polymerase gamma gene, the only polymerase present in human mitochondria, develop rare genetic syndromes including parkinsonian symptoms and loss of SNc neurons. Taken together, there is mounting clear evidence implicating mitochondrial dysfunction as a key disease hallmark in idiopathic PD.

Mitochondrial dysfunction is tightly linked to genetic PD

14Although only roughly 10% of PD cases are associated with defined genetic alterations, the study of these familial PD (PARK) genes has led to major advances in our understanding of PD etiopathogenesis. While numerous PARK genes have been identified, several of these are directly linked to impaired mitochondrial function and integrity (Table 1).

15Mutations of the genes coding for PINK1 (PARK6) and Parkin (PARK2) are the most frequent causes of autosomal recessive early-onset PD. Their clinical manifestation is characterized by relatively pure motor symptomatology and L-DOPA responsiveness, which can be accompanied by dopamimetica associated dyskinesia, hyperreflexia, and sometimes psychiatric symptoms. Interestingly, histopathological examination of postmortem tissue indicates loss of SNc dopaminergic neurons and neurons in other brain regions normally vulnerable in idiopathic PD (e.g., locus coeruleus, nucleus basalis meynert). However, presence of aSYN inclusions, a hallmark of idiopathic PD, is not a consistent feature of these PD cases. At the cellular level, PINK1 and Parkin play key roles in mitochondrial quality control mechanisms and signaling cascades in response to mitochondrial damage. PINK1/Parkin can not only initiate mitophagy, but also control fission and fusion of mitochondria, promote the generation of mitochondria derived vesicles and induce mitochondrial biogenesis. In fibroblasts from PINK1 and Parkin familial PD cases, loss of protein function leads to ETC impairment with reduced ATP production and high levels of ROS. While experimental studies using Parkin-KO mice revealed lower levels of mitochondrial respiratory capacity, PINK1-KO mice additionally exhibited defects in CI function, reduced Ca2+ buffering capacity, and impairments in mitochondrial membrane potential. Comparable findings have also been reported in Drosophila Parkin and PINK1 models. As the underlying pathophysiological event, increased mitochondrial fission has been identified in Parkin and PINK1 mutant mice and Drosophila models. This is supported by the fact that inhibition of mitochondrial fission via mdivi-1 treatment, was able to rescue mitochondrial function by normalizing the balance between mitochondrial fission and fusion. Apart from increased fission, defects in mitochondrial biogenesis have been shown to contribute to mitochondrial dysfunction in Parkin deficient human dopaminergic neurons.

16Interestingly, there is additional evidence for accumulation of insoluble Parkin within idiopathic PD patients. While previous studies observed that accumulating Parkin is S-nitrosylated, a more recent study discovered that Parkin itself functions as a redox molecule by providing antioxidant capacity for human midbrain neurons. Subsequent oxidizing posttranslational modifications then contribute to the decrease in Parkin solubility.

17Another example indicating mitochondrial driven parkinsonism, are mutations in the gene coding for DJ1 (PARK7). Resulting loss of function leads to an autosomal recessive form of PD which is less common than PINK1 or Parkin familial PD. The clinical presentation of individuals with DJ1 mutations is characterized by early onset slow progressing parkinsonism, which is frequently accompanied by non-motor symptomatology (e.g., anxiety, cognitive decline, and psychotic symptoms), and good L-DOPA responsiveness. Notably, postmortem histopathological analysis revealed widespread cortical and subcortical LP and neurodegeneration. DJ1 is involved in counteracting oxidative stress and subsequent mitochondrial dysfunction under physiological conditions. In the experimental setting, DJ1 depletion leads to impaired mitochondrial respiration, high levels of intracellular ROS, compromised mitochondrial membrane potential, and altered mitochondrial morphology. Furthermore, mutated DJ1 is translocated from the cytosol into the mitochondrial matrix where it gets degraded. Despite the increasing interest in DJ1’s function, the molecular mechanisms remain incompletely understood. Several lines of evidence suggest that DJ1 is a redox-sensitive protein which relies on cysteine oxidation to sense oxidative stress and then counteract this stress through activation of different signaling pathways. Other reports suggest that DJ1 may additionally possess chaperone activity, supported by data showing that DJ1 is able to attenuate aSYN aggregation, and the observation that human induced pluripotent stem cells (IPSCs) derived from fibroblasts of DJ1 PD patients exhibit increased aSYN pathology. However, further evidence highlights DJ1’s enzymatic functions, including glyoxalase and deglycase activities, showing that DJ1 can decrease reactive carbonyl products and repair glycated nucleic acids. Albeit the exact biological interplay of these processes is still debated, DJ1 clearly links antioxidant pathways, mitochondrial dysfunction, and aSYN aggregation.

18More recently mutations affecting vacuolar protein sorting 35 (VPS35 = PARK17) have been linked to late-onset autosomal dominant PD, and VPS13C (PARK23) to early onset rapid progressing autosomal recessive PD. Although the exact pathophysiological mechanisms are still intensively debated, experimental studies on VPS35 mutant fibroblasts, mice, or cell culture systems reported increased mitochondrial fragmentation, disturbed mitochondrial fission and fusion dynamics, and abnormal configuration of ETC CI. Mechanistically, VPS35 is a part of the retromer complex and thereby plays an important role in endosomal sorting and trafficking of proteins. VPS35 mutations have been shown to lead to an enhanced interaction of VPS35 with DLP1, which subsequently causes increased turnover of mitochondrial DLP1 complex, thereby fueling excessive mitochondrial fission, finally culminating in mitochondrial dysfunction and fragmentation. Further, VPS13C mutations have been shown to decrease mitochondrial membrane potential, promote mitochondrial fragmentation, and elevate mitophagy. In addition, mutations in FBXO7 (PARK15), causing a rare syndrome of juvenile parkinsonism with pyramidal signs, have been linked to impaired mitophagy and decreased CI function.

19Taken together, the familial PD cases not only show us that there is a clear link between genetic PD and mitochondrial dysfunction, they also highlight that multiple mitochondrial pathways may be impaired, including CI function, mitophagy, fission and fusion, and mitochondrial biogenesis.

Causal link between α-synuclein pathology and mitochondrial dysfunction

20While for a portion of PD patients, the occurrence of mitochondrial dysfunction can be explained by PARK genes, the etiology of idiopathic PD is still a matter of intensive debate. However, broad experimental evidence stemming from observations in isolated mitochondria, and rodents, suggests aSYN pathology as a major source of mitochondrial dysfunction (Fig. 2). Under physiological conditions, monomeric aSYN was shown to modulate the function of the mitochondrial ATP synthase subunit alpha, as aSYN knock-out mice showed reduced ATP synthase efficiency and reduced ATP levels. Similarly, another study employing aSYN deficient mice observed an altered neuronal mitochondrial membrane structure and CI deficiency.

21In the presence of aSYN pathology, meaning excessive amounts of overexpressed monomeric aSYN or existence of oligomeric and fibrillar aSYN, several studies reported decreased mitochondrial CI activity, alterations of mitochondrial membrane potential, and elevated oxidative stress levels. The effect on CI is further substantiated by another study which reported a dose-dependent effect of aSYN pathology on CI inhibition. Based on the observation that aSYN knock-out mice were resistant to MPTP induced toxicity, it has been hypothesized that aSYN directly influences CI function. This view is supported by studies which reported that overexpression of human aSYN in wildtype mice or use of SNCA A30P mutated transgenic mice worsened MPTP induced toxicity. Similar findings have also been observed for the CI inhibitor rotenone. However, CI does not seem to be the only engagement point for aSYN pathology. More recently, interaction of pathological aSYN oligomers with the ATP synthase subunit alpha in combination with mitochondrial permeability transition pore opening has been suggested as a mediator of aSYN induced mitochondrial dysfunction. Further, it has been shown that aSYN oligomers interact with the outer mitochondrial membrane protein TOM20. As a consequence of aSYN binding to TOM20, mitochondrial protein import is impaired causing ETC malfunction, accumulation of ROS and loss of mitochondrial membrane potential. aSYN induced loosening of contacts between mitochondria and the endoplasmic reticulum (ER), which are considered essential for proper Ca2+ exchange between those two organelles, has been reported as another possible cause of reduced mitochondrial respiration, primarily by dysregulated intracellular Ca2+ levels.

22Taken together, these studies not only show that aSYN pathology can trigger mitochondrial dysfunction, they reveal that there are several independent pathways how aSYN pathology affects mitochondrial function (Fig. 2). Notably, many of those pathways converge to a shared pathological phenotype exhibiting increased cellular and mitochondrial ROS, impairment of mitochondrial membrane potential, and reduced mitochondrial respiration.

Pathways linking mitochondrial dysfunction to neurodegeneration

23Does mitochondrial dysfunction cause neurodegeneration in PD, or is it simply a disease tombstone?

24While this question is difficult to answer for idiopathic PD, important information can be gleaned again from familial PD cases by looking at those few histopathological postmortem reports which are available. Notably, PINK1 as well as Parkin, and DJ1 mutation carriers, all familial PD cases where PD is thought to be majorly driven by mitochondrial dysfunction, exhibit marked neuronal cell loss within the SNc and other susceptible brain regions. This clearly indicates that at least genetically driven mitochondrial dysfunction is causative of neuronal cell loss in these individuals. This is supported by the finding that targeted disruption of mitochondrial CI in mice leads to dopaminergic degeneration culminating in a human-like type of parkinsonism. However, what is less clear is whether mitochondrial dysfunction is necessary for PD.

25As mentioned above, mitochondrial dysfunction and damage can contribute to several pathological cascades implicated in PD. As shown by using direct ratiometric probes, many at-risk neurons have been found to manifest elevated levels of mitochondrial oxidant stress. Sustained oxidant stress damages membranes, proteins, and DNA. This damage elevates mitophagy in SNc dopaminergic neurons, thereby diminishing the overall autophagic capacity. Cytosolic ROS can further damage proteins of the mitophagy pathway and increase mitochondrial dysfunction. Mitochondrially-generated ROS also compromises lysosomal and proteasomal function and increases the accumulation of misfolded forms of aSYN. Further, intracellular ROS triggers induction of parthanatos, an apoptosis independent pathway of neurodegeneration. In parallel, damaged mitochondria or excessive mitochondrial stress can induce mtDNA release into the cytosol and subsequent increases in the production of proinflammatory cytokines, as shown in Parkin-KO mice which also exhibited a POLG mutation. Mitochondrial dysfunction is further connected to neuroinflammation by the observation that loss of PINK1 and Parkin function results in increased mitochondrial antigen presentation and subsequent activation of cytotoxic T-cells. Intestinal infection with Gram-negative bacteria in PINK1 mice enhanced mitochondrial antigen presentation which was followed by elevated levels of CD8+ T-cells in the brain and periphery.

26As indicated above, failure of mitochondrial quality control mechanisms defines another pathway to neurodegeneration in PD. Substantial evidence shows that the concerted interplay of PINK1 and Parkin is essential for maintaining mitochondrial health. Loss of function mutations result in disruption of cellular mitophagy, as well as impaired fusion and fission of mitochondria, and reduced generation of mitochondrial derived vesicles. As a consequence, damaged mitochondria accumulate, cytochrome c and other proapoptotic proteins are released into the cytosol, and apoptosis might be induced. Damaged mitochondria due to loss of mitochondrial quality control mechanisms also contribute to the generation of oxidative stress and mtDNA mutations. Importantly, in idiopathic PD, LP also directly inactivates Parkin and thereby contributes to failure of mitochondrial quality control even in the absence of genetic mutations.

27Intracellular Ca2+ signaling also may contribute to pathogenesis. At-risk neurons have low intrinsic Ca2+ buffering capacity and strong engagement of both plasma membrane and ER-dependent Ca2+ signaling, leading to large cytosolic oscillations in intracellular Ca2+ concentration. Elevated intracellular Ca2+ can promote aSYN misfolding and aggregation thereby linking aSYN and Ca2+ in a vicious cycle.

28Another key hallmark of PD is impaired cellular proteasomal and lysosomal mechanisms. Proteasomal degradation as well as lysosomal function are energy consuming processes. It is easy to infer that compromised ATP production by mitochondria will reduce their functional capacity. Thus, elevated mitochondrial ROS production – and the resulting cellular damage – not only increases the burden on these systems, but with declining mitochondrial capacity it will likely diminish their capacity. As a consequence, not only aSYN aggregation is promoted but clearance of oxidized proteins is reduced, leading to further generation of ROS and oxidative damage in terms of a feedforward mechanism. Moreover, there is evidence for dynamic mitochondria-lysosome contacts which allow inter-organelle crosstalk. Interestingly, patient derived neurons harboring a heterozygous mutation within the gene coding for β-glucocerebrosidase (GBA1) show disturbed loosening of these contact sites which resulted in prolonged tethering and disruption of intracellular mitochondrial distribution.

29Taken together, current evidence indicates that there are several mitochondrial pathways which are tightly linked to other pathogenic mechanisms of PD. While some of these pathways are highly interdependent, others act in parallel to each other. From a translational standpoint, this suggests that, as in cancer, new therapeutic approaches will either need to target several of these pathways at once or be tailored to pathological endpoints shared by these pathways.

Therapeutic approaches targeting mitochondrial dysfunction in PD

30One of the greatest challenges facing the biomedical community is the development of a disease-modifying therapy for PD. Several clinical trials have been attempted to address this challenge, but none have succeeded. Several have targeted mitochondrial function either directly or indirectly.

31Given the recognition that mitochondrial oxidant stress is a potential driver of pathogenesis, some of the earliest trials aimed at reducing it (Table 2). For example, the antioxidant coenzyme Q10 (CoQ10) was tested in several trials, as was minocycline; they all failed. Mitochondrially-targeted antioxidants, like MitoQ, MitoVitE, MitoApocynin and MitoTEMPOL were developed to achieve better target engagement and showed promise in pre-clinical experiments, but this general strategy has not shown a clear benefit in PD patients. One of the key issues with these trials is that it is difficult to demonstrate adequate target engagement and biological efficacy of these compounds in humans. So, it is unclear whether they are testing the core hypothesis or not.

32A related approach is to try and boost brain concentrations of glutathione (Table 2). Nigral levels of glutathione are lower in PD patients, possibly because of an increased reliance upon glycolysis for ATP production in PD patients. Elevating glutathione has been proposed and explored in preclinical and clinical trials. However, it is unclear whether this is simply an effect of mitochondrial dysfunction and whether adequate brain concentrations can be achieved with oral dosing. N-Acetyl cysteine (NAC), an approved drug to treat acetaminophen induced liver failure, increases cellular glutathione levels in vivo. Notably, weekly intravenous administration of NAC over 3 months in idiopathic PD patients revealed a significant clinical improvement which was paralleled by increased dopamine transporter binding during ioflupane imaging (DaTSCAN).

33Another consequence of mitochondrial dysfunction is a lowering of nicotinamide adenine dinucleotide (NAD). Mitochondrial CI metabolizes NADH to NAD+. Boosting cellular NAD levels by dietary supplements of the precursor nicotinamide (vitamin B3) has neuroprotective effects in some preclinical models of PD. The recent phase I study NADPARK in which drug naïve de novo PD patients received 1000 mg of nicotinamide riboside over 30 days achieved some desired metabolic outcomes and a mild clinical benefit.

34A related approach is based upon epidemiological studies showing reduced risk of developing PD when using antidiabetic drugs like exenatide or pioglitazone. Both drugs have been studied intensively in preclinical animal models and clinical PD trials (Table 3). Exenatide appears to exert its neuroprotective effects by dampening neuroinflammatory pathways, reduction of ROS, lowering intracellular Ca2+ levels, restoring mitophagy, and improving overall bioenergetic efficiency. In a randomized double-blind placebo-controlled trial on PD patients under symptomatic dopamine replacement therapy, 48 weeks of exenatide, slightly although significantly, improved motor symptoms. Currently, a phase III trial is investigating the effects of a two-year exenatide treatment on motor symptoms in PD patients, which are again also receiving symptomatic dopamine replacement therapy. In contrast, 52 weeks long treatment with liraglutide, also a glucagon-like peptide 1 (GLP-1) agonist, resulted in improvement of non-motor symptoms and activities of daily living while motor symptoms were unchanged. While preclinical models suggest a mitochondria-based mechanism of action, there is no robust data from clinical studies regarding GLP-1 agonist’s cellular mechanism of action.

35Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, also has been considerably studied in PD. In animal studies, it reduced neuroinflammation, suppressed nitric oxide synthase activity, improved proteasomal clearance, and enhanced mitochondrial biogenesis. However, a phase II clinical trial in early PD patients found no clinical benefit of 44 weeks treatment with pioglitazone on disease progression.

36As outlined above, mitochondria are highly dynamic organelles that form a complex network within the cell soma, axon and down to the synaptic buttons. Maintaining this network in a viable state relies on constant spatial redistribution via mitochondrial trafficking, as well as balanced mitochondrial fusion and fission, to keep a pool of healthy mitochondria at any time. However, many of these mitochondrial quality control processes appear to be disrupted in PD patients. Based on that, several preclinical approaches have been developed to correct this putative defect in mitochondrial dynamics (Table 3). Inhibition of mitochondrial fission via the mitochondrial division inhibitor 1 (mdivi-1) has been reported to be neuroprotective in an aSYN overexpression rat model. Treatment with mdivi-1, reduced mitochondrial fragmentation and was simultaneously associated with reduced oxidative stress and improved mitochondrial health. Further, accumulation of the mitochondrial adaptor protein Miro on the outer mitochondrial membrane has been identified in PD and linked to delayed mitophagy in experimental PD models. Pharmacological reduction of Miro in cellular and PD Drosophila fly models was able to restore mitophagy and decrease neuronal cell loss.

37Further, gene therapy approaches targeting PINK1 and Parkin deficiencies have been explored (Table 3). PINK1 overexpression not only ameliorated mitochondrial dysfunction resulting from prior induced PINK1 deficiency in PINK1 mutant Drosophila models, but also was protective in an aSYN induced phenotype in aSYN transgenic Drosophila PD model, and protected against neuronal loss and mitochondrial dysfunction in in vitro and in vivo MPTP models. Overexpression of parkin has similar effects. A protein-based therapy using a cell-permeable Parkin was protective in 6-hydroxydopamine (6-OHDA) and adeno-associated viral vector (AAV) mouse models, presumably by enhancing mitochondrial quality control via facilitating mitochondrial biogenesis, and promoting mitophagy. It should be noted however that the predictive validity of both the 6-OHDA and MPTP models of PD is questionable, as all of the failed drugs have passed this test in preclinical work.

Limiting mitochondrial stimulation as a new therapeutic approach

38As outlined above, most of the mitochondrially-targeted, disease-modifying strategies that have moved to clinical trials, or are in the planning stages, are aimed at either limiting the consequences of mitochondrial damage (e.g., CoQ10), enhancing the clearance of damaged mitochondria (e.g., Miro targeting) or blunting the inflammatory consequences of mitochondrial dysfunction (e.g., exenatide). An alternative strategy is to first diminish mitochondrial damage. The mechanistic studies focusing on the origins of mitochondrial oxidant stress in at-risk neurons (like SNc dopaminergic neurons) point to their feedforward stimulation by plasma membrane L-type Ca2+ channels. Inhibiting L-type channels with dihydropyridine negative allosteric modulators lowered mitochondrial oxidant stress and mitophagy in at-risk dopaminergic neurons in animal models. They also diminished mitochondrial oxidant stress in a model of recessive PD, and showed neuroprotective effects in the MPTP and 6-OHDA models of PD. More importantly, epidemiological studies have shown that use of dihydropyridines is associated with a reduced risk of developing PD. These observations motivated two clinical trials with the dihydropyridine isradipine. Isradipine was chosen for these trials because it has the highest relative affinity for the sub-class of L-type channel thought to be the most important in driving mitochondrial stress in SNc dopaminergic neurons (channels with a pore-forming Cav1.3 subunit). While initial reports stated that there was no evidence of efficacy in modifying disease progression, a subsequent re-analysis reopened the discussion on an extended release formulation of isradipine, suggesting that there may be a disease modifying effect based on the UPDRS assessed progression in patients given 10 mg isradipine per day.

Current gaps in our understanding

39Based on our current knowledge of mitochondrial dysfunction in PD, there are at least four major gaps in our understanding.

40First, the chain of events arising from mitochondrial dysfunction needs to be more rigorously characterized. As in modern cancer treatment, this would allow combination therapies that maximize biological efficacy and minimize unwanted side-effects of treatment (see Tables 2 and 3).

41Second, there need to be more objective, and quantitative measures of disease progression. The reliance upon highly variable clinical rating scales adds an enormous amount of noise to clinical trial outcomes and prevents modest disease-modifying effects to be resolved. These biomarkers should include ones that assess mitochondrial function and dysfunction. Current strategies are mainly focused on improving neuroimaging of cellular bioenergetics (e.g., magnetic resonance spectroscopy). However, studies should also implement blood- or CSF-based biomarkers as recently demonstrated.

42Third, we need to have a better understanding of the mitochondrial pathways leading to neurodegeneration in the different PD subtypes. This could allow personalized disease-modification therapies and better target engagement.

43Fourth, we need to know whether the mechanisms driving disease progression in PD are time invariant or not. It could be that mitochondrial dysfunction is important in the early stages of PD pathogenesis, but not in later stages. For example, the later stages of cell loss in PD could be driven by network dysfunction caused by less than complete disruption of at-risk neuron function. A clear understanding of these mechanisms would allow disease-modifying treatments to be tailored to the respective disease stage.

Conclusions

44Mitochondrial dysfunction is a core hallmark of PD. Preclinical, epidemiological, histopathological, and clinical trial data point towards mitochondrial dysfunction as being a significant disease driving factor in idiopathic and familial PD. On the cellular level, core features are CI impairment, increased oxidative stress, disturbed mitochondrial quality control mechanisms, and bioenergetic deficiency. Current experimental evidence indicates that there are several mitochondrial pathways that contribute to PD pathogenesis. Targeting more than one of these pathways at the same time may be a more effective strategy than trying to affect just one. Moreover, given that the pathology in PD is largely in the brain, drug delivery strategies that optimize brain delivery and target engagement need to be pursued. So, while no treatment has been unequivocally shown to slow disease progression in the early stage of PD, there remains optimism that this situation will change soon.

References 287

1.
Bloem BR, Okun MS, Klein C. Parkinson's disease. Lancet. 2021;397:2284-2303.
Not in our library10.1016/s0140-6736(21)00218-x (opens in a new tab)
2.
Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE, et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. 2015;30:1591-1601.
Not in our library10.1002/mds.26424 (opens in a new tab)
3.
Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, Schrag AE, Lang AE. Parkinson disease. Nat Rev Dis Primers. 2017;3:17013.
Not in our library10.1038/nrdp.2017.13 (opens in a new tab)
4.
Chaudhuri KR, Healy DG, Schapira AH. National Institute for clinical E: non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol. 2006;5:235-245.
Not in our library10.1016/s1474-4422(06)70373-8 (opens in a new tab)
5.
Surmeier DJ, Obeso JA, Halliday GM. Selective neuronal vulnerability in Parkinson disease. Nat Rev Neurosci. 2017;18:101-113.
Not in our library10.1038/nrn.2016.178 (opens in a new tab)
6.
Neuropathology and molecular diagnosis of Synucleinopathies · 2021
No notice
7.
Beach TG, Adler CH, Sue LI, Vedders L, Lue L, White Iii CL, Akiyama H, Caviness JN, Shill HA, Sabbagh MN, et al. Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol. 2010;119:689-702.
Not in our library10.1007/s00401-010-0664-3 (opens in a new tab)
8.
Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. 2003;24:197-211.
Not in our library10.1016/s0197-4580(02)00065-9 (opens in a new tab)
9.
Dermal phospho-alpha-synuclein deposits confirm REM sleep behaviour disorder as prodromal Parkinson’s disease · 2017
No notice
10.
Luk KC, Kehm V, Carroll J, Zhang B, O'Brien P, Trojanowski JQ, Lee VM. Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science. 2012;338:949-953.
Not in our library10.1126/science.1227157 (opens in a new tab)
11.
The roles of connectivity and neuronal phenotype in determining the pattern of α-synuclein pathology in Parkinson's disease · 2022
Not checked
12.
On Cell Loss and Selective Vulnerability of Neuronal Populations in Parkinson's Disease · 2018
No notice
13.
Kalia LV, Lang AE. Parkinson's disease. Lancet. 2015;386:896-912.
Not in our library10.1016/s0140-6736(14)61393-3 (opens in a new tab)
14.
Hirsch EC, Standaert DG. Ten unsolved questions about Neuroinflammation in Parkinson's disease. Mov Disord. 2021;36:16-24.
Not in our library10.1002/mds.28075 (opens in a new tab)
15.
Sahoo S, Padhy AA, Kumari V, Mishra P. Role of ubiquitin-proteasome and autophagy-lysosome pathways in alpha-Synuclein aggregate clearance. Mol Neurobiol. 2022;59:5379-5407.
Not in our library10.1007/s12035-022-02897-1 (opens in a new tab)
16.
Wong YC, Luk K, Purtell K, Burke Nanni S, Stoessl AJ, Trudeau LE, Yue Z, Krainc D, Oertel W, Obeso JA, Volpicelli-Daley LA. Neuronal vulnerability in Parkinson disease: should the focus be on axons and synaptic terminals? Mov Disord. 2019;34:1406-1422.
Not in our library10.1002/mds.27823 (opens in a new tab)
17.
Yellen G. Fueling thought: management of glycolysis and oxidative phosphorylation in neuronal metabolism. J Cell Biol. 2018;217:2235-2246.
Not in our library10.1083/jcb.201803152 (opens in a new tab)
18.
Spinelli JB, Haigis MC. The multifaceted contributions of mitochondria to cellular metabolism. Nat Cell Biol. 2018;20:745-754.
Not in our library10.1038/s41556-018-0124-1 (opens in a new tab)
19.
Chakrabarty RP, Chandel NS. Mitochondria as signaling organelles control mammalian stem cell fate. Cell Stem Cell. 2021;28:394-408.
Not in our library10.1016/j.stem.2021.02.011 (opens in a new tab)
20.
Matsuda W, Furuta T, Nakamura KC, Hioki H, Fujiyama F, Arai R, Kaneko T. Single nigrostriatal dopaminergic neurons form widely spread and highly dense axonal arborizations in the neostriatum. J Neurosci. 2009;29:444-453.
Not in our library10.1523/jneurosci.4029-08.2009 (opens in a new tab)
21.
Area-Gomez E, Guardia-Laguarta C, Schon EA, Przedborski S. Mitochondria, OxPhos, and neurodegeneration: cells are not just running out of gas. J Clin Invest. 2019;129:34-45.
Not in our library10.1172/jci120848 (opens in a new tab)
22.
MFF-dependent mitochondrial fission regulates presynaptic release and axon branching by limiting axonal mitochondria size · 2018
No notice
23.
Living on the edge with too many mouths to feed: Why dopamine neurons die · 2012
No notice
24.
Pacelli C, Giguere N, Bourque MJ, Levesque M, Slack RS, Trudeau LE. Elevated mitochondrial bioenergetics and axonal Arborization size are key contributors to the vulnerability of dopamine neurons. Curr Biol. 2015;25:2349-2360.
Not in our library10.1016/j.cub.2015.07.050 (opens in a new tab)
25.
Martinez-Gonzalez C, Bolam JP, Mena-Segovia J. Topographical organization of the pedunculopontine nucleus. Front Neuroanat. 2011;5:22.
Not in our library10.3389/fnana.2011.00022 (opens in a new tab)
26.
Aston-Jones G, Waterhouse B. Locus coeruleus: from global projection system to adaptive regulation of behavior. Brain Res. 2016;1645:75-78.
Not in our library10.1016/j.brainres.2016.03.001 (opens in a new tab)
27.
Guzman JN, Sanchez-Padilla J, Chan CS, Surmeier DJ. Robust pacemaking in substantia nigra dopaminergic neurons. J Neurosci. 2009;29:11011-11019.
Not in our library10.1523/jneurosci.2519-09.2009 (opens in a new tab)
28.
Chan CS, Guzman JN, Ilijic E, Mercer JN, Rick C, Tkatch T, Meredith GE, Surmeier DJ. Rejuvenation' protects neurons in mouse models of Parkinson's disease. Nature. 2007;447:1081-1086.
Not in our library10.1038/nature05865 (opens in a new tab)
29.
Surmeier DJ, Guzman JN, Sanchez J, Schumacker PT. Physiological phenotype and vulnerability in Parkinson's disease. Cold Spring Harb Perspect Med. 2012;2:a009290.
Not in our library10.1101/cshperspect.a009290 (opens in a new tab)
30.
Sanchez-Padilla J, Guzman JN, Ilijic E, Kondapalli J, Galtieri DJ, Yang B, Schieber S, Oertel W, Wokosin D, Schumacker PT, Surmeier DJ. Mitochondrial oxidant stress in locus coeruleus is regulated by activity and nitric oxide synthase. Nat Neurosci. 2014;17:832-840.
Not in our library10.1038/nn.3717 (opens in a new tab)
31.
Goldberg JA, Guzman JN, Estep CM, Ilijic E, Kondapalli J, Sanchez-Padilla J, Surmeier DJ. Calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in Parkinson's disease. Nat Neurosci. 2012;15:1414-1421.
Not in our library10.1038/nn.3209 (opens in a new tab)
32.
Zampese E, Wokosin DL, Gonzalez-Rodriguez P, Guzman JN, Tkatch T, Kondapalli J, Surmeier WC, D'Alessandro KB, De Stefani D, Rizzuto R, et al. Ca(2+) channels couple spiking to mitochondrial metabolism in substantia nigra dopaminergic neurons. Sci Adv. 2022;8:eabp8701.
Not in our library10.1126/sciadv.abp8701 (opens in a new tab)
33.
Angelova PR, Abramov AY. Role of mitochondrial ROS in the brain: from physiology to neurodegeneration. FEBS Lett. 2018;592:692-702.
Not in our library10.1002/1873-3468.12964 (opens in a new tab)
34.
Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science. 1983;219:979-980.
Not in our library10.1126/science.6823561 (opens in a new tab)
35.
Dauer W, Przedborski S. Parkinson's disease: mechanisms and models. Neuron. 2003;39:889-909.
Not in our library10.1016/s0896-6273(03)00568-3 (opens in a new tab)
36.
Desai VG, Feuers RJ, Hart RW, Ali SF. MPP(+)-induced neurotoxicity in mouse is age-dependent: evidenced by the selective inhibition of complexes of electron transport. Brain Res. 1996;715:1-8.
Not in our library10.1016/0006-8993(95)01255-9 (opens in a new tab)
37.
Nicklas WJ, Vyas I, Heikkila RE. Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-pyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. Life Sci. 1985;36:2503-2508.
Not in our library10.1016/0024-3205(85)90146-8 (opens in a new tab)
38.
Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM, Kopin IJ. A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci U S A. 1983;80:4546-4550.
Not in our library10.1073/pnas.80.14.4546 (opens in a new tab)
39.
Meredith GE, Rademacher DJ. MPTP mouse models of Parkinson's disease: an update. J Parkinsons Dis. 2011;1:19-33.
Not in our library10.3233/jpd-2011-11023 (opens in a new tab)
40.
Hoglinger GU, Feger J, Prigent A, Michel PP, Parain K, Champy P, Ruberg M, Oertel WH, Hirsch EC. Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats. J Neurochem. 2003;84:491-502.
Not in our library10.1046/j.1471-4159.2003.01533.x (opens in a new tab)
41.
Pan-Montojo F, Schwarz M, Winkler C, Arnhold M, O'Sullivan GA, Pal A, Said J, Marsico G, Verbavatz JM, Rodrigo-Angulo M, et al. Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice. Sci Rep. 2012;2:898.
Not in our library10.1038/srep00898 (opens in a new tab)
42.
Martinez TN, Greenamyre JT. Toxin models of mitochondrial dysfunction in Parkinson's disease. Antioxid Redox Signal. 2012;16:920-934.
Not in our library10.1089/ars.2011.4033 (opens in a new tab)
43.
Gonzalez-Rodriguez P, Zampese E, Stout KA, Guzman JN, Ilijic E, Yang B, Tkatch T, Stavarache MA, Wokosin DL, Gao L, et al. Disruption of mitochondrial complex I induces progressive parkinsonism. Nature. 2021;599:650-656.
Not in our library10.1038/s41586-021-04059-0 (opens in a new tab)
44.
Schapira AH, Cooper JM, Dexter D, Jenner P, Clark JB, Marsden CD. Mitochondrial complex I deficiency in Parkinson's disease. Lancet. 1989;1:1269.
Not in our library10.1016/s0140-6736(89)92366-0 (opens in a new tab)
45.
Mann VM, Cooper JM, Krige D, Daniel SE, Schapira AH, Marsden CD. Brain, skeletal muscle and platelet homogenate mitochondrial function in Parkinson's disease. Brain. 1992;115(Pt 2):333-342.
Not in our library10.1093/brain/115.2.333 (opens in a new tab)
46.
Janetzky B, Hauck S, Youdim MB, Riederer P, Jellinger K, Pantucek F, Zochling R, Boissl KW, Reichmann H. Unaltered aconitase activity, but decreased complex I activity in substantia nigra pars compacta of patients with Parkinson's disease. Neurosci Lett. 1994;169:126-128.
Not in our library10.1016/0304-3940(94)90372-7 (opens in a new tab)
47.
Subrahmanian N, LaVoie MJ. Is there a special relationship between complex I activity and nigral neuronal loss in Parkinson's disease? A critical reappraisal. Brain Res. 2021;1767:147434.
Not in our library10.1016/j.brainres.2021.147434 (opens in a new tab)
48.
Flones IH, Fernandez-Vizarra E, Lykouri M, Brakedal B, Skeie GO, Miletic H, Lilleng PK, Alves G, Tysnes OB, Haugarvoll K, et al. Neuronal complex I deficiency occurs throughout the Parkinson's disease brain, but is not associated with neurodegeneration or mitochondrial DNA damage. Acta Neuropathol. 2018;135:409-425.
Not in our library10.1007/s00401-017-1794-7 (opens in a new tab)
49.
Mizuno Y, Ohta S, Tanaka M, Takamiya S, Suzuki K, Sato T, Oya H, Ozawa T, Kagawa Y. Deficiencies in complex I subunits of the respiratory chain in Parkinson's disease. Biochem Biophys Res Commun. 1989;163:1450-1455.
Not in our library10.1016/0006-291x(89)91141-8 (opens in a new tab)
50.
Hattori N, Tanaka M, Ozawa T, Mizuno Y. Immunohistochemical studies on complexes I, II, III, and IV of mitochondria in Parkinson's disease. Ann Neurol. 1991;30:563-571.
Not in our library10.1002/ana.410300409 (opens in a new tab)
51.
Ozawa T, Tanaka M, Ikebe S, Ohno K, Kondo T, Mizuno Y. Quantitative determination of deleted mitochondrial DNA relative to normal DNA in parkinsonian striatum by a kinetic PCR analysis. Biochem Biophys Res Commun. 1990;172:483-489.
Not in our library10.1016/0006-291x(90)90698-m (opens in a new tab)
52.
Lestienne P, Nelson J, Riederer P, Jellinger K, Reichmann H. Normal mitochondrial genome in brain from patients with Parkinson's disease and complex I defect. J Neurochem. 1990;55:1810-1812.
Not in our library10.1111/j.1471-4159.1990.tb04973.x (opens in a new tab)
53.
Mann VM, Cooper JM, Schapira AH. Quantitation of a mitochondrial DNA deletion in Parkinson's disease. FEBS Lett. 1992;299:218-222.
Not in our library10.1016/0014-5793(92)80118-z (opens in a new tab)
54.
Gu G, Reyes PE, Golden GT, Woltjer RL, Hulette C, Montine TJ, Zhang J. Mitochondrial DNA deletions/rearrangements in parkinson disease and related neurodegenerative disorders. J Neuropathol Exp Neurol. 2002;61:634-639.
Not in our library10.1093/jnen/61.7.634 (opens in a new tab)
55.
Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, Jaros E, Hersheson JS, Betts J, Klopstock T, et al. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet. 2006;38:515-517.
Not in our library10.1038/ng1769 (opens in a new tab)
56.
Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease · 2016
No notice
57.
Rahman S, Copeland WC. POLG-related disorders and their neurological manifestations. Nat Rev Neurol. 2019;15:40-52.
Not in our library10.1038/s41582-018-0101-0 (opens in a new tab)
58.
Sulzer D, Edwards RH. The physiological role of alpha-synuclein and its relationship to Parkinson's disease. J Neurochem. 2019;150:475-486.
Not in our library10.1111/jnc.14810 (opens in a new tab)
59.
Devi L, Raghavendran V, Prabhu BM, Avadhani NG, Anandatheerthavarada HK. Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain. J Biol Chem. 2008;283:9089-9100.
Not in our library10.1074/jbc.m710012200 (opens in a new tab)
60.
Li L, Nadanaciva S, Berger Z, Shen W, Paumier K, Schwartz J, Mou K, Loos P, Milici AJ, Dunlop J, Hirst WD. Human A53T alpha-synuclein causes reversible deficits in mitochondrial function and dynamics in primary mouse cortical neurons. PLoS One. 2013;8:e85815.
Not in our library10.1371/journal.pone.0085815 (opens in a new tab)
61.
Arias-Fuenzalida J, Jarazo J, Qing X, Walter J, Gomez-Giro G, Nickels SL, Zaehres H, Scholer HR, Schwamborn JC. FACS-assisted CRISPR-Cas9 genome editing facilitates Parkinson's disease modeling. Stem Cell Rep. 2017;9:1423-1431.
Not in our library10.1016/j.stemcr.2017.08.026 (opens in a new tab)
62.
Subramaniam SR, Vergnes L, Franich NR, Reue K, Chesselet MF. Region specific mitochondrial impairment in mice with widespread overexpression of alpha-synuclein. Neurobiol Dis. 2014;70:204-213.
Not in our library10.1016/j.nbd.2014.06.017 (opens in a new tab)
63.
Tapias V, Hu X, Luk KC, Sanders LH, Lee VM, Greenamyre JT. Synthetic alpha-synuclein fibrils cause mitochondrial impairment and selective dopamine neurodegeneration in part via iNOS-mediated nitric oxide production. Cell Mol Life Sci. 2017;74:2851-2874.
Not in our library10.1007/s00018-017-2541-x (opens in a new tab)
64.
Ludtmann MH, Angelova PR, Ninkina NN, Gandhi S, Buchman VL, Abramov AY. Monomeric alpha-Synuclein exerts a physiological role on brain ATP synthase. J Neurosci. 2016;36:10510-10521.
Not in our library10.1523/jneurosci.1659-16.2016 (opens in a new tab)
65.
Ellis CE, Murphy EJ, Mitchell DC, Golovko MY, Scaglia F, Barcelo-Coblijn GC, Nussbaum RL. Mitochondrial lipid abnormality and electron transport chain impairment in mice lacking alpha-synuclein. Mol Cell Biol. 2005;25:10190-10201.
Not in our library10.1128/mcb.25.22.10190-10201.2005 (opens in a new tab)
66.
Hsu LJ, Sagara Y, Arroyo A, Rockenstein E, Sisk A, Mallory M, Wong J, Takenouchi T, Hashimoto M, Masliah E. Alpha-synuclein promotes mitochondrial deficit and oxidative stress. Am J Pathol. 2000;157:401-410.
Not in our library10.1016/s0002-9440(10)64553-1 (opens in a new tab)
67.
PINK1 and Parkin mitochondrial quality control: a source of regional vulnerability in Parkinson’s disease · 2020
No notice
68.
Kamienieva I, Duszynski J, Szczepanowska J. Multitasking guardian of mitochondrial quality: Parkin function and Parkinson's disease. Transl Neurodegener. 2021;10:5.
Not in our library10.1186/s40035-020-00229-8 (opens in a new tab)
69.
Pickrell AM, Youle RJ. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease. Neuron. 2015;85:257-273.
Not in our library10.1016/j.neuron.2014.12.007 (opens in a new tab)
70.
Lazarou M, Sliter DA, Kane LA, Sarraf SA, Wang C, Burman JL, Sideris DP, Fogel AI, Youle RJ. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature. 2015;524:309-314.
Not in our library10.1038/nature14893 (opens in a new tab)
71.
Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature. 2006;441:1162-1166.
Not in our library10.1038/nature04779 (opens in a new tab)
72.
Gautier CA, Kitada T, Shen J. Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress. Proc Natl Acad Sci U S A. 2008;105:11364-11369.
Not in our library10.1073/pnas.0802076105 (opens in a new tab)
73.
PINK1-Associated Parkinson's Disease Is Caused by Neuronal Vulnerability to Calcium-Induced Cell Death · 2009
No notice
74.
Thomas KJ, McCoy MK, Blackinton J, Beilina A, van der Brug M, Sandebring A, Miller D, Maric D, Cedazo-Minguez A, Cookson MR. DJ-1 acts in parallel to the PINK1/parkin pathway to control mitochondrial function and autophagy. Hum Mol Genet. 2011;20:40-50.
Not in our library10.1093/hmg/ddq430 (opens in a new tab)
75.
Liu Y, Ma X, Fujioka H, Liu J, Chen S, Zhu X. DJ-1 regulates the integrity and function of ER-mitochondria association through interaction with IP3R3-Grp75-VDAC1. Proc Natl Acad Sci U S A. 2019;116:25322-25328.
Not in our library10.1073/pnas.1906565116 (opens in a new tab)
76.
Shtifman A, Zhong N, Lopez JR, Shen J, Xu J. Altered Ca2+ homeostasis in the skeletal muscle of DJ-1 null mice. Neurobiol Aging. 2011;32:125-132.
Not in our library10.1016/j.neurobiolaging.2009.07.010 (opens in a new tab)
77.
Taipa R, Pereira C, Reis I, Alonso I, Bastos-Lima A, Melo-Pires M, Magalhaes M. DJ-1 linked parkinsonism (PARK7) is associated with Lewy body pathology. Brain. 2016;139:1680-1687.
Not in our library10.1093/brain/aww080 (opens in a new tab)
78.
Irrcher I, Aleyasin H, Seifert EL, Hewitt SJ, Chhabra S, Phillips M, Lutz AK, Rousseaux MW, Bevilacqua L, Jahani-Asl A, et al. Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics. Hum Mol Genet. 2010;19:3734-3746.
Not in our library10.1093/hmg/ddq288 (opens in a new tab)
79.
Wang X, Petrie TG, Liu Y, Liu J, Fujioka H, Zhu X. Parkinson's disease-associated DJ-1 mutations impair mitochondrial dynamics and cause mitochondrial dysfunction. J Neurochem. 2012;121:830-839.
Not in our library10.1111/j.1471-4159.2012.07734.x (opens in a new tab)
80.
Giaime E, Yamaguchi H, Gautier CA, Kitada T, Shen J. Loss of DJ-1 does not affect mitochondrial respiration but increases ROS production and mitochondrial permeability transition pore opening. PLoS One. 2012;7:e40501.
Not in our library10.1371/journal.pone.0040501 (opens in a new tab)
81.
Kuhlmann N, Milnerwood AJ. A critical LRRK at the synapse? The neurobiological function and pathophysiological dysfunction of LRRK2. Front Mol Neurosci. 2020;13:153.
Not in our library10.3389/fnmol.2020.00153 (opens in a new tab)
82.
Bonet-Ponce L, Cookson MR. LRRK2 recruitment, activity, and function in organelles. FEBS J. 2022;289:6871-6890.
Not in our library10.1111/febs.16099 (opens in a new tab)
83.
Rocha EM, Keeney MT, Di Maio R, De Miranda BR, Greenamyre JT. LRRK2 and idiopathic Parkinson's disease. Trends Neurosci. 2022;45:224-236.
Not in our library10.1016/j.tins.2021.12.002 (opens in a new tab)
84.
Tolosa E, Vila M, Klein C, Rascol O. LRRK2 in Parkinson disease: challenges of clinical trials. Nat Rev Neurol. 2020;16:97-107.
Not in our library10.1038/s41582-019-0301-2 (opens in a new tab)
85.
Heo HY, Park JM, Kim CH, Han BS, Kim KS, Seol W. LRRK2 enhances oxidative stress-induced neurotoxicity via its kinase activity. Exp Cell Res. 2010;316:649-656.
Not in our library10.1016/j.yexcr.2009.09.014 (opens in a new tab)
86.
Singh A, Zhi L, Zhang H. LRRK2 and mitochondria: recent advances and current views. Brain Res. 2019;1702:96-104.
Not in our library10.1016/j.brainres.2018.06.010 (opens in a new tab)
87.
Xiao B, Deng X, Ng EY, Allen JC, Lim SY, Ahmad-Annuar A, Tan EK. Association of LRRK2 haplotype with age at onset in Parkinson disease. JAMA Neurol. 2018;75:127-128.
Not in our library10.1001/jamaneurol.2017.3363 (opens in a new tab)
88.
Luth T, Konig IR, Grunewald A, Kasten M, Klein C, Hentati F, Farrer M, Trinh J. Age at onset of LRRK2 p.Gly2019Ser is related to environmental and lifestyle factors. Mov Disord. 2020;35:1854-1858.
Not in our library10.1002/mds.28238 (opens in a new tab)
89.
van Veen S, Martin S, Van den Haute C, Benoy V, Lyons J, Vanhoutte R, Kahler JP, Decuypere JP, Gelders G, Lambie E, et al. ATP13A2 deficiency disrupts lysosomal polyamine export. Nature. 2020;578:419-424.
Not in our library10.1038/s41586-020-1968-7 (opens in a new tab)
90.
Fujii T, Nagamori S, Wiriyasermkul P, Zheng S, Yago A, Shimizu T, Tabuchi Y, Okumura T, Fujii T, Takeshima H, Sakai H. Parkinson's disease-associated ATP13A2/PARK9 functions as a lysosomal H(+),K(+)-ATPase. Nat Commun. 2023;14:2174.
Not in our library10.1038/s41467-023-37815-z (opens in a new tab)
91.
Ramirez A, Heimbach A, Grundemann J, Stiller B, Hampshire D, Cid LP, Goebel I, Mubaidin AF, Wriekat AL, Roeper J, et al. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat Genet. 2006;38:1184-1191.
Not in our library10.1038/ng1884 (opens in a new tab)
92.
Vrijsen S, Besora-Casals L, van Veen S, Zielich J, Van den Haute C, Hamouda NN, Fischer C, Ghesquiere B, Tournev I, Agostinis P, et al. ATP13A2-mediated endo-lysosomal polyamine export counters mitochondrial oxidative stress. Proc Natl Acad Sci U S A. 2020;117:31198-31207.
Not in our library10.1073/pnas.1922342117 (opens in a new tab)
93.
Dehay B, Ramirez A, Martinez-Vicente M, Perier C, Canron MH, Doudnikoff E, Vital A, Vila M, Klein C, Bezard E. Loss of P-type ATPase ATP13A2/PARK9 function induces general lysosomal deficiency and leads to Parkinson disease neurodegeneration. Proc Natl Acad Sci U S A. 2012;109:9611-9616.
Not in our library10.1073/pnas.1112368109 (opens in a new tab)
94.
Joseph S, Schulz JB, Stegmuller J. Mechanistic contributions of FBXO7 to Parkinson disease. J Neurochem. 2018;144:118-127.
Not in our library10.1111/jnc.14253 (opens in a new tab)
95.
Burchell VS, Nelson DE, Sanchez-Martinez A, Delgado-Camprubi M, Ivatt RM, Pogson JH, Randle SJ, Wray S, Lewis PA, Houlden H, et al. The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy. Nat Neurosci. 2013;16:1257-1265.
Not in our library10.1038/nn.3489 (opens in a new tab)
96.
Zhou ZD, Xie SP, Sathiyamoorthy S, Saw WT, Sing TY, Ng SH, Chua HP, Tang AM, Shaffra F, Li Z, et al. F-box protein 7 mutations promote protein aggregation in mitochondria and inhibit mitophagy. Hum Mol Genet. 2015;24:6314-6330.
Not in our library10.1093/hmg/ddv340 (opens in a new tab)
97.
Delgado-Camprubi M, Esteras N, Soutar MP, Plun-Favreau H, Abramov AY. Deficiency of Parkinson's disease-related gene Fbxo7 is associated with impaired mitochondrial metabolism by PARP activation. Cell Death Differ. 2017;24:2210.
Not in our library10.1038/cdd.2017.175 (opens in a new tab)
98.
Sassone J, Reale C, Dati G, Regoni M, Pellecchia MT, Garavaglia B. The role of VPS35 in the pathobiology of Parkinson's disease. Cell Mol Neurobiol. 2021;41:199-227.
Not in our library10.1007/s10571-020-00849-8 (opens in a new tab)
99.
Williams ET, Chen X, Otero PA, Moore DJ. Understanding the contributions of VPS35 and the retromer in neurodegenerative disease. Neurobiol Dis. 2022;170:105768.
Not in our library10.1016/j.nbd.2022.105768 (opens in a new tab)
100.
Lesage S, Drouet V, Majounie E, Deramecourt V, Jacoupy M, Nicolas A, Cormier-Dequaire F, Hassoun SM, Pujol C, Ciura S, et al. Loss of VPS13C function in autosomal-recessive parkinsonism causes mitochondrial dysfunction and increases PINK1/Parkin-dependent Mitophagy. Am J Hum Genet. 2016;98:500-513.
Not in our library10.1016/j.ajhg.2016.01.014 (opens in a new tab)
101.
Wang W, Wang X, Fujioka H, Hoppel C, Whone AL, Caldwell MA, Cullen PJ, Liu J, Zhu X. Parkinson's disease-associated mutant VPS35 causes mitochondrial dysfunction by recycling DLP1 complexes. Nat Med. 2016;22:54-63.
Not in our library10.1038/nm.3983 (opens in a new tab)
102.
Tang FL, Liu W, Hu JX, Erion JR, Ye J, Mei L, Xiong WC. VPS35 deficiency or mutation causes dopaminergic neuronal loss by impairing mitochondrial fusion and function. Cell Rep. 2015;12:1631-1643.
Not in our library10.1016/j.celrep.2015.08.001 (opens in a new tab)
103.
Zhou L, Wang W, Hoppel C, Liu J, Zhu X. Parkinson's disease-associated pathogenic VPS35 mutation causes complex I deficits. Biochim Biophys Acta Mol basis Dis. 2017;1863:2791-2795.
Not in our library10.1016/j.bbadis.2017.07.032 (opens in a new tab)
104.
Ruan Y, Hu J, Che Y, Liu Y, Luo Z, Cheng J, Han Q, He H, Zhou Q. CHCHD2 and CHCHD10 regulate mitochondrial dynamics and integrated stress response. Cell Death Dis. 2022;13:156.
Not in our library10.1038/s41419-022-04602-5 (opens in a new tab)
105.
Kee TR, Espinoza Gonzalez P, Wehinger JL, Bukhari MZ, Ermekbaeva A, Sista A, Kotsiviras P, Liu T, Kang DE, Woo JA. Mitochondrial CHCHD2: disease-associated mutations, physiological functions, and current animal models. Front Aging Neurosci. 2021;13:660843.
Not in our library10.3389/fnagi.2021.660843 (opens in a new tab)
106.
Ikeda A, Nishioka K, Meng H, Takanashi M, Hasegawa I, Inoshita T, Shiba-Fukushima K, Li Y, Yoshino H, Mori A, et al. Mutations in CHCHD2 cause alpha-synuclein aggregation. Hum Mol Genet. 2019;28:3895-3911.
Not in our library10.1093/hmg/ddz241 (opens in a new tab)
107.
Liu YT, Huang X, Nguyen D, Shammas MK, Wu BP, Dombi E, Springer DA, Poulton J, Sekine S, Narendra DP. Loss of CHCHD2 and CHCHD10 activates OMA1 peptidase to disrupt mitochondrial cristae phenocopying patient mutations. Hum Mol Genet. 2020;29:1547-1567.
Not in our library10.1093/hmg/ddaa077 (opens in a new tab)
108.
Sato S, Noda S, Torii S, Amo T, Ikeda A, Funayama M, Yamaguchi J, Fukuda T, Kondo H, Tada N, et al. Homeostatic p62 levels and inclusion body formation in CHCHD2 knockout mice. Hum Mol Genet. 2021;30:443-453.
Not in our library10.1093/hmg/ddab057 (opens in a new tab)
109.
Kumar N, Leonzino M, Hancock-Cerutti W, Horenkamp FA, Li P, Lees JA, Wheeler H, Reinisch KM, De Camilli P. VPS13A and VPS13C are lipid transport proteins differentially localized at ER contact sites. J Cell Biol. 2018;217:3625-3639.
Not in our library10.1083/jcb.201807019 (opens in a new tab)
110.
ER-lysosome lipid transfer protein VPS13C/PARK23 prevents aberrant mtDNA-dependent STING signaling · 2022
No notice
111.
Samaranch L, Lorenzo-Betancor O, Arbelo JM, Ferrer I, Lorenzo E, Irigoyen J, Pastor MA, Marrero C, Isla C, Herrera-Henriquez J, Pastor P. PINK1-linked parkinsonism is associated with Lewy body pathology. Brain. 2010;133:1128-1142.
Not in our library10.1093/brain/awq051 (opens in a new tab)
112.
Pramstaller PP, Schlossmacher MG, Jacques TS, Scaravilli F, Eskelson C, Pepivani I, Hedrich K, Adel S, Gonzales-McNeal M, Hilker R, et al. Lewy body Parkinson's disease in a large pedigree with 77 Parkin mutation carriers. Ann Neurol. 2005;58:411-422.
Not in our library10.1002/ana.20587 (opens in a new tab)
113.
Steele JC, Guella I, Szu-Tu C, Lin MK, Thompson C, Evans DM, Sherman HE, Vilarino-Guell C, Gwinn K, Morris H, et al. Defining neurodegeneration on Guam by targeted genomic sequencing. Ann Neurol. 2015;77:458-468.
Not in our library10.1002/ana.24346 (opens in a new tab)
114.
Takanashi M, Li Y, Hattori N. Absence of Lewy pathology associated with PINK1 homozygous mutation. Neurology. 2016;86:2212-2213.
Not in our library10.1212/wnl.0000000000002744 (opens in a new tab)
115.
Houlden H, Singleton AB. The genetics and neuropathology of Parkinson's disease. Acta Neuropathol. 2012;124:325-338.
Not in our library10.1007/s00401-012-1013-5 (opens in a new tab)
116.
Schneider SA, Alcalay RN. Neuropathology of genetic synucleinopathies with parkinsonism: review of the literature. Mov Disord. 2017;32:1504-1523.
Not in our library10.1002/mds.27193 (opens in a new tab)
117.
Deng H, Dodson MW, Huang H, Guo M. The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc Natl Acad Sci U S A. 2008;105:14503-14508.
Not in our library10.1073/pnas.0803998105 (opens in a new tab)
118.
Yang Y, Ouyang Y, Yang L, Beal MF, McQuibban A, Vogel H, Lu B. Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery. Proc Natl Acad Sci U S A. 2008;105:7070-7075.
Not in our library10.1073/pnas.0711845105 (opens in a new tab)
119.
Soubannier V, McLelland GL, Zunino R, Braschi E, Rippstein P, Fon EA, McBride HM. A vesicular transport pathway shuttles cargo from mitochondria to lysosomes. Curr Biol. 2012;22:135-141.
Not in our library10.1016/j.cub.2011.11.057 (opens in a new tab)
120.
McLelland GL, Lee SA, McBride HM, Fon EA. Syntaxin-17 delivers PINK1/parkin-dependent mitochondrial vesicles to the endolysosomal system. J Cell Biol. 2016;214:275-291.
Not in our library10.1083/jcb.201603105 (opens in a new tab)
121.
Kumar M, Acevedo-Cintron J, Jhaldiyal A, Wang H, Andrabi SA, Eacker S, Karuppagounder SS, Brahmachari S, Chen R, Kim H, et al. Defects in mitochondrial biogenesis drive mitochondrial alterations in PARKIN-deficient human dopamine neurons. Stem Cell Rep. 2020;15:629-645.
Not in our library10.1016/j.stemcr.2020.07.013 (opens in a new tab)
122.
Abramov AY, Smulders-Srinivasan TK, Kirby DM, Acin-Perez R, Enriquez JA, Lightowlers RN, Duchen MR, Turnbull DM. Mechanism of neurodegeneration of neurons with mitochondrial DNA mutations. Brain. 2010;133:797-807.
Not in our library10.1093/brain/awq015 (opens in a new tab)
123.
Rakovic A, Grunewald A, Seibler P, Ramirez A, Kock N, Orolicki S, Lohmann K, Klein C. Effect of endogenous mutant and wild-type PINK1 on Parkin in fibroblasts from Parkinson disease patients. Hum Mol Genet. 2010;19:3124-3137.
Not in our library10.1093/hmg/ddq215 (opens in a new tab)
124.
Mortiboys H, Thomas KJ, Koopman WJ, Klaffke S, Abou-Sleiman P, Olpin S, Wood NW, Willems PH, Smeitink JA, Cookson MR, Bandmann O. Mitochondrial function and morphology are impaired in parkin-mutant fibroblasts. Ann Neurol. 2008;64:555-565.
Not in our library10.1002/ana.21492 (opens in a new tab)
125.
Palacino JJ, Sagi D, Goldberg MS, Krauss S, Motz C, Wacker M, Klose J, Shen J. Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem. 2004;279:18614-18622.
Not in our library10.1074/jbc.m401135200 (opens in a new tab)
126.
Periquet M, Corti O, Jacquier S, Brice A. Proteomic analysis of parkin knockout mice: alterations in energy metabolism, protein handling and synaptic function. J Neurochem. 2005;95:1259-1276.
Not in our library10.1111/j.1471-4159.2005.03442.x (opens in a new tab)
127.
Stichel CC, Zhu XR, Bader V, Linnartz B, Schmidt S, Lubbert H. Mono- and double-mutant mouse models of Parkinson's disease display severe mitochondrial damage. Hum Mol Genet. 2007;16:2377-2393.
Not in our library10.1093/hmg/ddm083 (opens in a new tab)
128.
Regulation of mitochondrial permeability transition pore by PINK1 · 2012
Not checked
129.
Heeman B, Van den Haute C, Aelvoet SA, Valsecchi F, Rodenburg RJ, Reumers V, Debyser Z, Callewaert G, Koopman WJ, Willems PH, Baekelandt V. Depletion of PINK1 affects mitochondrial metabolism, calcium homeostasis and energy maintenance. J Cell Sci. 2011;124:1115-1125.
Not in our library10.1242/jcs.078303 (opens in a new tab)
130.
Morais VA, Verstreken P, Roethig A, Smet J, Snellinx A, Vanbrabant M, Haddad D, Frezza C, Mandemakers W, Vogt-Weisenhorn D, et al. Parkinson's disease mutations in PINK1 result in decreased complex I activity and deficient synaptic function. EMBO Mol Med. 2009;1:99-111.
Not in our library10.1002/emmm.200900006 (opens in a new tab)
131.
Increased Mitochondrial Calcium Sensitivity and Abnormal Expression of Innate Immunity Genes Precede Dopaminergic Defects in Pink1-Deficient Mice · 2011
No notice
132.
Greene JC, Whitworth AJ, Kuo I, Andrews LA, Feany MB, Pallanck LJ. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci U S A. 2003;100:4078-4083.
Not in our library10.1073/pnas.0737556100 (opens in a new tab)
133.
Park J, Lee SB, Lee S, Kim Y, Song S, Kim S, Bae E, Kim J, Shong M, Kim JM, Chung J. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature. 2006;441:1157-1161.
Not in our library10.1038/nature04788 (opens in a new tab)
134.
Whitworth AJ, Theodore DA, Greene JC, Benes H, Wes PD, Pallanck LJ. Increased glutathione S-transferase activity rescues dopaminergic neuron loss in a Drosophila model of Parkinson's disease. Proc Natl Acad Sci U S A. 2005;102:8024-8029.
Not in our library10.1073/pnas.0501078102 (opens in a new tab)
135.
Gao Q, Tian R, Han H, Slone J, Wang C, Ke X, Zhang T, Li X, He Y, Liao P, et al. PINK1-mediated Drp1(S616) phosphorylation modulates synaptic development and plasticity via promoting mitochondrial fission. Signal Transduct Target Ther. 2022;7:103.
Not in our library10.1038/s41392-022-00933-z (opens in a new tab)
136.
Cui M, Tang X, Christian WV, Yoon Y, Tieu K. Perturbations in mitochondrial dynamics induced by human mutant PINK1 can be rescued by the mitochondrial division inhibitor mdivi-1. J Biol Chem. 2010;285:11740-11752.
Not in our library10.1074/jbc.m109.066662 (opens in a new tab)
137.
Schlossmacher MG, Frosch MP, Gai WP, Medina M, Sharma N, Forno L, Ochiishi T, Shimura H, Sharon R, Hattori N, et al. Parkin localizes to the Lewy bodies of Parkinson disease and dementia with Lewy bodies. Am J Pathol. 2002;160:1655-1667.
Not in our library10.1016/s0002-9440(10)61113-3 (opens in a new tab)
138.
LaVoie MJ, Ostaszewski BL, Weihofen A, Schlossmacher MG, Selkoe DJ. Dopamine covalently modifies and functionally inactivates parkin. Nat Med. 2005;11:1214-1221.
Not in our library10.1038/nm1314 (opens in a new tab)
139.
Chung KK, Thomas B, Li X, Pletnikova O, Troncoso JC, Marsh L, Dawson VL, Dawson TM. S-nitrosylation of parkin regulates ubiquitination and compromises parkin's protective function. Science. 2004;304:1328-1331.
Not in our library10.1126/science.1093891 (opens in a new tab)
140.
Sunico CR, Nakamura T, Rockenstein E, Mante M, Adame A, Chan SF, Newmeyer TF, Masliah E, Nakanishi N, Lipton SA. S-Nitrosylation of parkin as a novel regulator of p53-mediated neuronal cell death in sporadic Parkinson's disease. Mol Neurodegener. 2013;8:29.
Not in our library10.1186/1750-1326-8-29 (opens in a new tab)
141.
Tokarew JM, El-Kodsi DN, Lengacher NA, Fehr TK, Nguyen AP, Shutinoski B, O'Nuallain B, Jin M, Khan JM, Ng ACH, et al. Age-associated insolubility of parkin in human midbrain is linked to redox balance and sequestration of reactive dopamine metabolites. Acta Neuropathol. 2021;141:725-754.
Not in our library10.1007/s00401-021-02285-4 (opens in a new tab)
142.
Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F, Ibanez P, Joosse M, et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science. 2003;299:256-259.
Not in our library10.1126/science.1077209 (opens in a new tab)
143.
Reduced Basal Autophagy and Impaired Mitochondrial Dynamics Due to Loss of Parkinson's Disease-Associated Protein DJ-1 · 2010
No notice
144.
Andres-Mateos E, Perier C, Zhang L, Blanchard-Fillion B, Greco TM, Thomas B, Ko HS, Sasaki M, Ischiropoulos H, Przedborski S, et al. DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase. Proc Natl Acad Sci U S A. 2007;104:14807-14812.
Not in our library10.1073/pnas.0703219104 (opens in a new tab)
145.
Guzman JN, Sanchez-Padilla J, Wokosin D, Kondapalli J, Ilijic E, Schumacker PT, Surmeier DJ. Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. Nature. 2010;468:696-700.
Not in our library10.1038/nature09536 (opens in a new tab)
146.
Queliconi BB, Kojima W, Kimura M, Imai K, Udagawa C, Motono C, et al. Unfolding is the driving force for mitochondrial import and degradation of the Parkinson's disease-related protein DJ-1. J Cell Sci. 2021;134(22):jcs258653.
Not in our library10.1242/jcs.258653 (opens in a new tab)
147.
Kim RH, Peters M, Jang Y, Shi W, Pintilie M, Fletcher GC, DeLuca C, Liepa J, Zhou L, Snow B, et al. DJ-1, a novel regulator of the tumor suppressor PTEN. Cancer Cell. 2005;7:263-273.
Not in our library10.1016/j.ccr.2005.02.010 (opens in a new tab)
148.
Bahmed K, Messier EM, Zhou W, Tuder RM, Freed CR, Chu HW, Kelsen SG, Bowler RP, Mason RJ, Kosmider B. DJ-1 modulates nuclear erythroid 2-related Factor-2-mediated protection in human primary alveolar type II cells in smokers. Am J Respir Cell Mol Biol. 2016;55:439-449.
Not in our library10.1165/rcmb.2015-0304oc (opens in a new tab)
149.
Cao J, Ying M, Xie N, Lin G, Dong R, Zhang J, Yan H, Yang X, He Q, Yang B. The oxidation states of DJ-1 dictate the cell fate in response to oxidative stress triggered by 4-hpr: autophagy or apoptosis? Antioxid Redox Signal. 2014;21:1443-1459.
Not in our library10.1089/ars.2013.5446 (opens in a new tab)
150.
Lee SJ, Kim SJ, Kim IK, Ko J, Jeong CS, Kim GH, Park C, Kang SO, Suh PG, Lee HS, Cha SS. Crystal structures of human DJ-1 and Escherichia coli Hsp31, which share an evolutionarily conserved domain. J Biol Chem. 2003;278:44552-44559.
Not in our library10.1074/jbc.m304517200 (opens in a new tab)
151.
DJ-1 Is a Redox-Dependent Molecular Chaperone That Inhibits α-Synuclein Aggregate Formation · 2004
No notice
152.
DJ-1 interactions with α-synuclein attenuate aggregation and cellular toxicity in models of Parkinson’s disease · 2014
No notice
153.
Burbulla LF, Song P, Mazzulli JR, Zampese E, Wong YC, Jeon S, Santos DP, Blanz J, Obermaier CD, Strojny C, et al. Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's disease. Science. 2017;357:1255-1261.
Not in our library10.1126/science.aam9080 (opens in a new tab)
154.
Richarme G, Liu C, Mihoub M, Abdallah J, Leger T, Joly N, Liebart JC, Jurkunas UV, Nadal M, Bouloc P, et al. Guanine glycation repair by DJ-1/Park7 and its bacterial homologs. Science. 2017;357:208-211.
Not in our library10.1126/science.aag1095 (opens in a new tab)
155.
Mazza MC, Shuck SC, Lin J, Moxley MA, Termini J, Cookson MR, Wilson MA. DJ-1 is not a deglycase and makes a modest contribution to cellular defense against methylglyoxal damage in neurons. J Neurochem. 2022;162:245-261.
Not in our library10.1111/jnc.15656 (opens in a new tab)
156.
Vilarino-Guell C, Wider C, Ross OA, Dachsel JC, Kachergus JM, Lincoln SJ, Soto-Ortolaza AI, Cobb SA, Wilhoite GJ, Bacon JA, et al. VPS35 mutations in Parkinson disease. Am J Hum Genet. 2011;89:162-167.
Not in our library10.1016/j.ajhg.2011.06.001 (opens in a new tab)
157.
Zimprich A, Benet-Pages A, Struhal W, Graf E, Eck SH, Offman MN, Haubenberger D, Spielberger S, Schulte EC, Lichtner P, et al. A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease. Am J Hum Genet. 2011;89:168-175.
Not in our library10.1016/j.ajhg.2011.06.008 (opens in a new tab)
158.
Wang W, Ma X, Zhou L, Liu J, Zhu X. A conserved retromer sorting motif is essential for mitochondrial DLP1 recycling by VPS35 in Parkinson's disease model. Hum Mol Genet. 2017;26:781-789.
Not in our library10.1093/hmg/ddw430 (opens in a new tab)
159.
Luth ES, Stavrovskaya IG, Bartels T, Kristal BS, Selkoe DJ. Soluble, prefibrillar alpha-synuclein oligomers promote complex I-dependent, Ca2+−induced mitochondrial dysfunction. J Biol Chem. 2014;289:21490-21507.
Not in our library10.1074/jbc.m113.545749 (opens in a new tab)
160.
Chinta SJ, Mallajosyula JK, Rane A, Andersen JK. Mitochondrial alpha-synuclein accumulation impairs complex I function in dopaminergic neurons and results in increased mitophagy in vivo. Neurosci Lett. 2010;486:235-239.
Not in our library10.1016/j.neulet.2010.09.061 (opens in a new tab)
161.
Loeb V, Yakunin E, Saada A, Sharon R. The transgenic overexpression of alpha-synuclein and not its related pathology associates with complex I inhibition. J Biol Chem. 2010;285:7334-7343.
Not in our library10.1074/jbc.m109.061051 (opens in a new tab)
162.
Aggregated α-synuclein and complex I deficiency: exploration of their relationship in differentiated neurons · 2015
No notice
163.
Liu G, Zhang C, Yin J, Li X, Cheng F, Li Y, Yang H, Ueda K, Chan P, Yu S. Alpha-Synuclein is differentially expressed in mitochondria from different rat brain regions and dose-dependently down-regulates complex I activity. Neurosci Lett. 2009;454:187-192.
Not in our library10.1016/j.neulet.2009.02.056 (opens in a new tab)
164.
Klivenyi P, Siwek D, Gardian G, Yang L, Starkov A, Cleren C, Ferrante RJ, Kowall NW, Abeliovich A, Beal MF. Mice lacking alpha-synuclein are resistant to mitochondrial toxins. Neurobiol Dis. 2006;21:541-548.
Not in our library10.1016/j.nbd.2005.08.018 (opens in a new tab)
165.
Song DD, Shults CW, Sisk A, Rockenstein E, Masliah E. Enhanced substantia nigra mitochondrial pathology in human alpha-synuclein transgenic mice after treatment with MPTP. Exp Neurol. 2004;186:158-172.
Not in our library10.1016/s0014-4886(03)00342-x (opens in a new tab)
166.
Song LK, Ma KL, Yuan YH, Mu Z, Song XY, Niu F, Han N, Chen NH. Targeted overexpression of alpha-Synuclein by rAAV2/1 vectors induces progressive Nigrostriatal degeneration and increases vulnerability to MPTP in mouse. PLoS One. 2015;10:e0131281.
Not in our library10.1371/journal.pone.0131281 (opens in a new tab)
167.
Cannon JR, Geghman KD, Tapias V, Sew T, Dail MK, Li C, Greenamyre JT. Expression of human E46K-mutated alpha-synuclein in BAC-transgenic rats replicates early-stage Parkinson's disease features and enhances vulnerability to mitochondrial impairment. Exp Neurol. 2013;240:44-56.
Not in our library10.1016/j.expneurol.2012.11.007 (opens in a new tab)
168.
Shavali S, Brown-Borg HM, Ebadi M, Porter J. Mitochondrial localization of alpha-synuclein protein in alpha-synuclein overexpressing cells. Neurosci Lett. 2008;439:125-128.
Not in our library10.1016/j.neulet.2008.05.005 (opens in a new tab)
169.
α-synuclein oligomers interact with ATP synthase and open the permeability transition pore in Parkinson’s disease · 2018
No notice
170.
Di Maio R, Barrett PJ, Hoffman EK, Barrett CW, Zharikov A, Borah A, Hu X, McCoy J, Chu CT, Burton EA, et al. Alpha-Synuclein binds to TOM20 and inhibits mitochondrial protein import in Parkinson's disease. Sci Transl Med. 2016;8:342ra378.
Not in our library10.1126/scitranslmed.aaf3634 (opens in a new tab)
171.
Martinez JH, Fuentes F, Vanasco V, Alvarez S, Alaimo A, Cassina A, Coluccio Leskow F, Velazquez F. Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment. Arch Biochem Biophys. 2018;651:1-12.
Not in our library10.1016/j.abb.2018.04.018 (opens in a new tab)
172.
α-Synuclein binds to the ER–mitochondria tethering protein VAPB to disrupt Ca2+ homeostasis and mitochondrial ATP production · 2017
No notice
173.
Erustes AG, D'Eletto M, Guarache GC, Ureshino RP, Bincoletto C, da Silva Pereira GJ, Piacentini M, Smaili SS. Overexpression of alpha-synuclein inhibits mitochondrial ca(2+) trafficking between the endoplasmic reticulum and mitochondria through MAMs by altering the GRP75-IP3R interaction. J Neurosci Res. 2021;99:2932-2947.
Not in our library10.1002/jnr.24952 (opens in a new tab)
174.
Bose A, Beal MF. Mitochondrial dysfunction in Parkinson's disease. J Neurochem. 2016;139(Suppl 1):216-231.
Not in our library10.1111/jnc.13731 (opens in a new tab)
175.
Nicoletti V, Palermo G, Del Prete E, Mancuso M, Ceravolo R. Understanding the multiple role of mitochondria in Parkinson's disease and related disorders: lesson from genetics and protein-interaction network. Front Cell Dev Biol. 2021;9:636506.
Not in our library10.3389/fcell.2021.636506 (opens in a new tab)
176.
Guzman JN, Ilijic E, Yang B, Sanchez-Padilla J, Wokosin D, Galtieri D, Kondapalli J, Schumacker PT, Surmeier DJ. Systemic isradipine treatment diminishes calcium-dependent mitochondrial oxidant stress. J Clin Invest. 2018;128:2266-2280.
Not in our library10.1172/jci95898 (opens in a new tab)
177.
Perfeito R, Lazaro DF, Outeiro TF, Rego AC. Linking alpha-synuclein phosphorylation to reactive oxygen species formation and mitochondrial dysfunction in SH-SY5Y cells. Mol Cell Neurosci. 2014;62:51-59.
Not in our library10.1016/j.mcn.2014.08.002 (opens in a new tab)
178.
Kam TI, Mao X, Park H, Chou SC, Karuppagounder SS, Umanah GE, et al. Poly(ADP-ribose) drives pathologic alpha-synuclein neurodegeneration in Parkinson's disease. Science. 2018;362(6414):eaat8407.
Not in our library10.1126/science.aat8407 (opens in a new tab)
179.
Oka T, Hikoso S, Yamaguchi O, Taneike M, Takeda T, Tamai T, Oyabu J, Murakawa T, Nakayama H, Nishida K, et al. Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature. 2012;485:251-255.
Not in our library10.1038/nature10992 (opens in a new tab)
180.
West AP, Khoury-Hanold W, Staron M, Tal MC, Pineda CM, Lang SM, Bestwick M, Duguay BA, Raimundo N, MacDuff DA, et al. Mitochondrial DNA stress primes the antiviral innate immune response. Nature. 2015;520:553-557.
Not in our library10.1038/nature14156 (opens in a new tab)
181.
Sliter DA, Martinez J, Hao L, Chen X, Sun N, Fischer TD, Burman JL, Li Y, Zhang Z, Narendra DP, et al. Parkin and PINK1 mitigate STING-induced inflammation. Nature. 2018;561:258-262.
Not in our library10.1038/s41586-018-0448-9 (opens in a new tab)
182.
Matheoud D, Sugiura A, Bellemare-Pelletier A, Laplante A, Rondeau C, Chemali M, Fazel A, Bergeron JJ, Trudeau LE, Burelle Y, et al. Parkinson's disease-related proteins PINK1 and Parkin repress mitochondrial antigen presentation. Cell. 2016;166:314-327.
Not in our library10.1016/j.cell.2016.05.039 (opens in a new tab)
183.
Matheoud D, Cannon T, Voisin A, Penttinen AM, Ramet L, Fahmy AM, Ducrot C, Laplante A, Bourque MJ, Zhu L, et al. Intestinal infection triggers Parkinson's disease-like symptoms in Pink1(−/−) mice. Nature. 2019;571:565-569.
Not in our library10.1038/s41586-019-1405-y (opens in a new tab)
184.
Nath S, Goodwin J, Engelborghs Y, Pountney DL. Raised calcium promotes alpha-synuclein aggregate formation. Mol Cell Neurosci. 2011;46:516-526.
Not in our library10.1016/j.mcn.2010.12.004 (opens in a new tab)
185.
Han JY, Choi TS, Kim HI. Molecular role of ca(2+) and hard divalent metal cations on accelerated fibrillation and Interfibrillar aggregation of alpha-Synuclein. Sci Rep. 1895;2018:8.
Not in our library10.1038/s41598-018-20320-5 (opens in a new tab)
186.
McNaught KS, Belizaire R, Isacson O, Jenner P, Olanow CW. Altered proteasomal function in sporadic Parkinson's disease. Exp Neurol. 2003;179:38-46.
Not in our library10.1006/exnr.2002.8050 (opens in a new tab)
187.
Bukhatwa S, Zeng BY, Rose S, Jenner P. A comparison of changes in proteasomal subunit expression in the substantia nigra in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy. Brain Res. 2010;1326:174-183.
Not in our library10.1016/j.brainres.2010.02.045 (opens in a new tab)
188.
Dysregulation of mitochondria-lysosome contacts by GBA1 dysfunction in dopaminergic neuronal models of Parkinson’s disease · 2021
No notice
189.
Hargreaves IP, Lane A, Sleiman PM. The coenzyme Q10 status of the brain regions of Parkinson's disease patients. Neurosci Lett. 2008;447:17-19.
Not in our library10.1016/j.neulet.2008.09.069 (opens in a new tab)
190.
Younes-Mhenni S, Frih-Ayed M, Kerkeni A, Bost M, Chazot G. Peripheral blood markers of oxidative stress in Parkinson's disease. Eur Neurol. 2007;58:78-83.
Not in our library10.1159/000103641 (opens in a new tab)
191.
Ilic TV, Jovanovic M, Jovicic A, Tomovic M. Oxidative stress indicators are elevated in de novo Parkinson's disease patients. Funct Neurol. 1999;14:141-147.
Not in our library
192.
Littarru GP, Tiano L. Bioenergetic and antioxidant properties of coenzyme Q10: recent developments. Mol Biotechnol. 2007;37:31-37.
Not in our library10.1007/s12033-007-0052-y (opens in a new tab)
193.
Moon Y, Lee KH, Park JH, Geum D, Kim K. Mitochondrial membrane depolarization and the selective death of dopaminergic neurons by rotenone: protective effect of coenzyme Q10. J Neurochem. 2005;93:1199-1208.
Not in our library10.1111/j.1471-4159.2005.03112.x (opens in a new tab)
194.
Park HW, Park CG, Park M, Lee SH, Park HR, Lim J, Paek SH, Choy YB. Intrastriatal administration of coenzyme Q10 enhances neuroprotection in a Parkinson's disease rat model. Sci Rep. 2020;10:9572.
Not in our library10.1038/s41598-020-66493-w (opens in a new tab)
195.
Abdin AA, Hamouda HE. Mechanism of the neuroprotective role of coenzyme Q10 with or without L-dopa in rotenone-induced parkinsonism. Neuropharmacology. 2008;55:1340-1346.
Not in our library10.1016/j.neuropharm.2008.08.033 (opens in a new tab)
196.
Beal MF, Matthews RT, Tieleman A, Shults CW. Coenzyme Q10 attenuates the 1-methyl-4-phenyl-1,2,3,tetrahydropyridine (MPTP) induced loss of striatal dopamine and dopaminergic axons in aged mice. Brain Res. 1998;783:109-114.
Not in our library10.1016/s0006-8993(97)01192-x (opens in a new tab)
197.
Cleren C, Yang L, Lorenzo B, Calingasan NY, Schomer A, Sireci A, Wille EJ, Beal MF. Therapeutic effects of coenzyme Q10 (CoQ10) and reduced CoQ10 in the MPTP model of parkinsonism. J Neurochem. 2008;104:1613-1621.
Not in our library10.1111/j.1471-4159.2007.05097.x (opens in a new tab)
198.
Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, et al. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol. 2002;59:1541-1550.
Not in our library10.1001/archneur.59.10.1541 (opens in a new tab)
199.
Parkinson Study Group QEI, Beal MF, Oakes D, Shoulson I, Henchcliffe C, Galpern WR, Haas R, Juncos JL, Nutt JG, Voss TS, et al. A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol. 2014;71:543-552.
Not in our library10.1001/jamaneurol.2014.131 (opens in a new tab)
200.
Negida A, Menshawy A, El Ashal G, Elfouly Y, Hani Y, Hegazy Y, El Ghonimy S, Fouda S, Rashad Y. Coenzyme Q10 for patients with Parkinson's disease: a systematic review and Meta-analysis. CNS Neurol Disord Drug Targets. 2016;15:45-53.
Not in our library10.2174/1871527314666150821103306 (opens in a new tab)
201.
Noda N, Hamatani T, Shibue Y, Takagaki T, Kitamura A, Haranaka M, Ogama Y, Kakuyama H. Phase 1 study to investigate the safety, tolerability, and pharmacokinetics of EPI-589 in healthy participants. Clin Pharmacol Drug Dev. 2022;11:1136-1146.
Not in our library10.1002/cpdd.1146 (opens in a new tab)
202.
Prasuhn J, Kasten M, Vos M, Konig IR, Schmid SM, Wilms B, Klein C, Bruggemann N. The use of vitamin K2 in patients with Parkinson's disease and mitochondrial dysfunction (PD-K2): a Theranostic pilot study in a placebo-controlled parallel group design. Front Neurol. 2020;11:592104.
Not in our library10.3389/fneur.2020.592104 (opens in a new tab)
203.
Banerjee P, Saha I, Sarkar D, Maiti AK. Contributions and limitations of mitochondria-targeted and non-targeted antioxidants in the treatment of parkinsonism: an updated review. Neurotox Res. 2022;40:847-873.
Not in our library10.1007/s12640-022-00501-x (opens in a new tab)
204.
Ghosh A, Chandran K, Kalivendi SV, Joseph J, Antholine WE, Hillard CJ, Kanthasamy A, Kanthasamy A, Kalyanaraman B. Neuroprotection by a mitochondria-targeted drug in a Parkinson's disease model. Free Radic Biol Med. 2010;49:1674-1684.
Not in our library10.1016/j.freeradbiomed.2010.08.028 (opens in a new tab)
205.
Langley M, Ghosh A, Charli A, Sarkar S, Ay M, Luo J, Zielonka J, Brenza T, Bennett B, Jin H, et al. Mito-Apocynin prevents mitochondrial dysfunction, microglial activation, oxidative damage, and progressive neurodegeneration in MitoPark transgenic mice. Antioxid Redox Signal. 2017;27:1048-1066.
Not in our library10.1089/ars.2016.6905 (opens in a new tab)
206.
Ghosh A, Langley MR, Harischandra DS, Neal ML, Jin H, Anantharam V, Joseph J, Brenza T, Narasimhan B, Kanthasamy A, et al. Mitoapocynin treatment protects against Neuroinflammation and dopaminergic neurodegeneration in a preclinical animal model of Parkinson's disease. J NeuroImmune Pharmacol. 2016;11:259-278.
Not in our library10.1007/s11481-016-9650-4 (opens in a new tab)
207.
Snow BJ, Rolfe FL, Lockhart MM, Frampton CM, O'Sullivan JD, Fung V, Smith RA, Murphy MP, Taylor KM, Protect Study G. A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson's disease. Mov Disord. 2010;25:1670-1674.
Not in our library10.1002/mds.23148 (opens in a new tab)
208.
Poulter MO, Payne KB, Steiner JP. Neuroimmunophilins: a novel drug therapy for the reversal of neurodegenerative disease? Neuroscience. 2004;128:1-6.
Not in our library10.1016/j.neuroscience.2004.06.016 (opens in a new tab)
209.
Investigators. NN-P: a randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease. Neurology. 2007;68:20-8.
Not in our library10.1212/01.wnl.0000250355.28474.8e (opens in a new tab)
210.
Charisis S, Ntanasi E, Stamelou M, Xiromerisiou G, Maraki M, Veskoukis AS, Yannakoulia M, Kosmidis MH, Anastasiou CA, Giagkou N, et al. Plasma glutathione and prodromal Parkinson's disease probability. Mov Disord. 2022;37:200-205.
Not in our library10.1002/mds.28826 (opens in a new tab)
211.
Meister A. On the antioxidant effects of ascorbic acid and glutathione. Biochem Pharmacol. 1992;44:1905-1915.
Not in our library10.1016/0006-2952(92)90091-v (opens in a new tab)
212.
Zeevalk GD, Bernard LP, Guilford FT. Liposomal-glutathione provides maintenance of intracellular glutathione and neuroprotection in mesencephalic neuronal cells. Neurochem Res. 2010;35:1575-1587.
Not in our library10.1007/s11064-010-0217-0 (opens in a new tab)
213.
Mischley LK, Lau RC, Shankland EG, Wilbur TK, Padowski JM. Phase IIb study of intranasal glutathione in Parkinson's disease. J Parkinsons Dis. 2017;7:289-299.
Not in our library10.3233/jpd-161040 (opens in a new tab)
214.
Rahimmi A, Khosrobakhsh F, Izadpanah E, Moloudi MR, Hassanzadeh K. N-acetylcysteine prevents rotenone-induced Parkinson's disease in rat: an investigation into the interaction of parkin and Drp1 proteins. Brain Res Bull. 2015;113:34-40.
Not in our library10.1016/j.brainresbull.2015.02.007 (opens in a new tab)
215.
Caridade-Silva R, Araujo B, Martins-Macedo J, Teixeira FG. N-Acetylcysteine treatment may compensate motor impairments through dopaminergic transmission modulation in a striatal 6-Hydroxydopamine Parkinson's disease rat model. Antioxidants (Basel). 2023:12(6):1257.
Not in our library10.3390/antiox12061257 (opens in a new tab)
216.
Clark J, Clore EL, Zheng K, Adame A, Masliah E, Simon DK. Oral N-acetyl-cysteine attenuates loss of dopaminergic terminals in alpha-synuclein overexpressing mice. PLoS One. 2010;5:e12333.
Not in our library10.1371/journal.pone.0012333 (opens in a new tab)
217.
Monti DA, Zabrecky G, Kremens D, Liang TW, Wintering NA, Bazzan AJ, Zhong L, Bowens BK, Chervoneva I, Intenzo C, Newberg AB. N-acetyl cysteine is associated with dopaminergic improvement in Parkinson's disease. Clin Pharmacol Ther. 2019;106:884-890.
Not in our library10.1002/cpt.1548 (opens in a new tab)
218.
Lautrup S, Sinclair DA, Mattson MP, Fang EF. NAD(+) in brain aging and neurodegenerative disorders. Cell Metab. 2019;30:630-655.
Not in our library10.1016/j.cmet.2019.09.001 (opens in a new tab)
219.
Shan C, Gong YL, Zhuang QQ, Hou YF, Wang SM, Zhu Q, Huang GR, Tao B, Sun LH, Zhao HY, et al. Protective effects of beta- nicotinamide adenine dinucleotide against motor deficits and dopaminergic neuronal damage in a mouse model of Parkinson's disease. Prog Neuro-Psychopharmacol Biol Psychiatry. 2019;94:109670.
Not in our library10.1016/j.pnpbp.2019.109670 (opens in a new tab)
220.
Schondorf DC, Ivanyuk D, Baden P, Sanchez-Martinez A, De Cicco S, Yu C, Giunta I, Schwarz LK, Di Napoli G, Panagiotakopoulou V, et al. The NAD+ precursor nicotinamide riboside rescues mitochondrial defects and neuronal loss in iPSC and Fly models of Parkinson's disease. Cell Rep. 2018;23:2976-2988.
Not in our library10.1016/j.celrep.2018.05.009 (opens in a new tab)
221.
Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults · 2019
No notice
222.
Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults · 2018
No notice
223.
Brakedal B, Dolle C, Riemer F, Ma Y, Nido GS, Skeie GO, Craven AR, Schwarzlmuller T, Brekke N, Diab J, et al. The NADPARK study: a randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease. Cell Metab. 2022;34(396–407):e396.
Not in our library10.1016/j.cmet.2022.02.001 (opens in a new tab)
224.
Schlesinger I, Schlesinger N. Uric acid in Parkinson's disease. Mov Disord. 2008;23:1653-1657.
Not in our library10.1002/mds.22139 (opens in a new tab)
225.
Guerreiro S, Ponceau A, Toulorge D, Martin E, Alvarez-Fischer D, Hirsch EC, Michel PP. Protection of midbrain dopaminergic neurons by the end-product of purine metabolism uric acid: potentiation by low-level depolarization. J Neurochem. 2009;109:1118-1128.
Not in our library10.1111/j.1471-4159.2009.06040.x (opens in a new tab)
226.
Chen X, Burdett TC, Desjardins CA, Logan R, Cipriani S, Xu Y, Schwarzschild MA. Disrupted and transgenic urate oxidase alter urate and dopaminergic neurodegeneration. Proc Natl Acad Sci U S A. 2013;110:300-305.
Not in our library10.1073/pnas.1217296110 (opens in a new tab)
227.
Cipriani S, Bakshi R, Schwarzschild MA. Protection by inosine in a cellular model of Parkinson's disease. Neuroscience. 2014;274:242-249.
Not in our library10.1016/j.neuroscience.2014.05.038 (opens in a new tab)
228.
El-Shamarka MEA, Kozman MR, Messiha BAS. The protective effect of inosine against rotenone-induced Parkinson's disease in mice; role of oxido-nitrosative stress, ERK phosphorylation, and A2AR expression. Naunyn Schmiedeberg's Arch Pharmacol. 2020;393:1041-1053.
Not in our library10.1007/s00210-019-01804-1 (opens in a new tab)
229.
Khanal S, Bok E, Kim J, Park GH, Choi DY. Dopaminergic neuroprotective effects of inosine in MPTP-induced parkinsonian mice via brain-derived neurotrophic factor upregulation. Neuropharmacology. 2023;238:109652.
Not in our library10.1016/j.neuropharm.2023.109652 (opens in a new tab)
230.
El-Latif AMA, Rabie MA, Sayed RH, Fattah M, Kenawy SA. Inosine attenuates rotenone-induced Parkinson's disease in rats by alleviating the imbalance between autophagy and apoptosis. Drug Dev Res. 2023;84:1159-1174.
Not in our library10.1002/ddr.22077 (opens in a new tab)
231.
Parkinson Study Group S-PDI, Schwarzschild MA, Ascherio A, Beal MF, Cudkowicz ME, Curhan GC, Hare JM, Hooper DC, Kieburtz KD, Macklin EA, et al. Inosine to increase serum and cerebrospinal fluid urate in Parkinson disease: a randomized clinical trial. JAMA Neurol. 2014;71:141-150.
Not in our library10.1001/jamaneurol.2013.5528 (opens in a new tab)
232.
Parkinson Study Group S-PDI, Schwarzschild MA, Ascherio A, Casaceli C, Curhan GC, Fitzgerald R, Kamp C, Lungu C, Macklin EA, Marek K, et al. Effect of urate-elevating inosine on early Parkinson disease progression: the SURE-PD3 randomized clinical trial. JAMA. 2021;326:926-939.
Not in our library10.1001/jama.2021.10207 (opens in a new tab)
233.
Abdelkader NF, Safar MM, Salem HA. Ursodeoxycholic acid ameliorates apoptotic Cascade in the rotenone model of Parkinson's disease: modulation of mitochondrial perturbations. Mol Neurobiol. 2016;53:810-817.
Not in our library10.1007/s12035-014-9043-8 (opens in a new tab)
234.
Mortiboys H, Furmston R, Bronstad G, Aasly J, Elliott C, Bandmann O. UDCA exerts beneficial effect on mitochondrial dysfunction in LRRK2(G2019S) carriers and in vivo. Neurology. 2015;85:846-852.
Not in our library10.1212/wnl.0000000000001905 (opens in a new tab)
235.
Jiang C, Shen D, Li K, Wang H, Sang W, Qi H. Protective effects of Ursodeoxycholic acid against oxidative stress and Neuroinflammation through mitogen-activated protein kinases pathway in MPTP-induced Parkinson disease. Clin Neuropharmacol. 2022;45:168-174.
Not in our library10.1097/wnf.0000000000000528 (opens in a new tab)
236.
Qi H, Shen D, Jiang C, Wang H, Chang M. Ursodeoxycholic acid protects dopaminergic neurons from oxidative stress via regulating mitochondrial function, autophagy, and apoptosis in MPTP/MPP(+)-induced Parkinson's disease. Neurosci Lett. 2021;741:135493.
Not in our library10.1016/j.neulet.2020.135493 (opens in a new tab)
237.
Sathe AG, Tuite P, Chen C, Ma Y, Chen W, Cloyd J, Low WC, Steer CJ, Lee BY, Zhu XH, Coles LD. Pharmacokinetics, safety, and tolerability of orally administered Ursodeoxycholic acid in patients with Parkinson's disease-a pilot study. J Clin Pharmacol. 2020;60:744-750.
Not in our library10.1002/jcph.1575 (opens in a new tab)
238.
Klopstock T, Elstner M, Bender A. Creatine in mouse models of neurodegeneration and aging. Amino Acids. 2011;40:1297-1303.
Not in our library10.1007/s00726-011-0850-1 (opens in a new tab)
239.
Cankaya S, Cankaya B, Kilic U, Kilic E, Yulug B. The therapeutic role of minocycline in Parkinson's disease. Drugs Context. 2019;8:212553.
Not in our library10.7573/dic.212553 (opens in a new tab)
240.
Matthews RT, Ferrante RJ, Klivenyi P, Yang L, Klein AM, Mueller G, Kaddurah-Daouk R, Beal MF. Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp Neurol. 1999;157:142-149.
Not in our library10.1006/exnr.1999.7049 (opens in a new tab)
241.
Investigators. NN-P: a randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurology. 2006;66:664-71.
Not in our library10.1212/01.wnl.0000201252.57661.e1 (opens in a new tab)
242.
Dodel R, Spottke A, Gerhard A, Reuss A, Reinecker S, Schimke N, Trenkwalder C, Sixel-Doring F, Herting B, Kamm C, et al. Minocycline 1-year therapy in multiple-system-atrophy: effect on clinical symptoms and [(11)C] (R)-PK11195 PET (MEMSA-trial). Mov Disord. 2010;25:97-107.
Not in our library10.1002/mds.22732 (opens in a new tab)
243.
Sofic E, Riederer P, Heinsen H, Beckmann H, Reynolds GP, Hebenstreit G, Youdim MB. Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain. J Neural Transm. 1988;74:199-205.
Not in our library10.1007/bf01244786 (opens in a new tab)
244.
Meta-analysis of brain iron levels of Parkinson’s disease patients determined by postmortem and MRI measurements · 2016
No notice
245.
Dexter DT, Statton SA, Whitmore C, Freinbichler W, Weinberger P, Tipton KF, Della Corte L, Ward RJ, Crichton RR. Clinically available iron chelators induce neuroprotection in the 6-OHDA model of Parkinson's disease after peripheral administration. J Neural Transm (Vienna). 2011;118:223-231.
Not in our library10.1007/s00702-010-0531-3 (opens in a new tab)
246.
Kaur D, Yantiri F, Rajagopalan S, Kumar J, Mo JQ, Boonplueang R, Viswanath V, Jacobs R, Yang L, Beal MF, et al. Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease. Neuron. 2003;37:899-909.
Not in our library10.1016/s0896-6273(03)00126-0 (opens in a new tab)
247.
Workman DG, Tsatsanis A, Lewis FW, Boyle JP, Mousadoust M, Hettiarachchi NT, Hunter M, Peers CS, Tetard D, Duce JA. Protection from neurodegeneration in the 6-hydroxydopamine (6-OHDA) model of Parkinson's with novel 1-hydroxypyridin-2-one metal chelators. Metallomics. 2015;7:867-876.
Not in our library10.1039/c4mt00326h (opens in a new tab)
248.
Molina-Holgado F, Gaeta A, Francis PT, Williams RJ, Hider RC. Neuroprotective actions of deferiprone in cultured cortical neurones and SHSY-5Y cells. J Neurochem. 2008;105:2466-2476.
Not in our library10.1111/j.1471-4159.2008.05332.x (opens in a new tab)
249.
Brain iron chelation by deferiprone in a phase 2 randomised double-blinded placebo controlled clinical trial in Parkinson’s disease · 2017
No notice
250.
Devos D, Moreau C, Devedjian JC, Kluza J, Petrault M, Laloux C, Jonneaux A, Ryckewaert G, Garcon G, Rouaix N, et al. Targeting chelatable iron as a therapeutic modality in Parkinson's disease. Antioxid Redox Signal. 2014;21:195-210.
Not in our library10.1089/ars.2013.5593 (opens in a new tab)
251.
Devos D, Labreuche J, Rascol O, Corvol JC, Duhamel A, Guyon Delannoy P, Poewe W, Compta Y, Pavese N, Ruzicka E, et al. Trial of Deferiprone in Parkinson's disease. N Engl J Med. 2022;387:2045-2055.
Not in our library10.1056/nejmoa2209254 (opens in a new tab)
252.
Elkouzi A, Vedam-Mai V, Eisinger RS, Okun MS. Emerging therapies in Parkinson disease - repurposed drugs and new approaches. Nat Rev Neurol. 2019;15:204-223.
Not in our library10.1038/s41582-019-0155-7 (opens in a new tab)
253.
Targeting Mitochondrial Impairment in Parkinson's Disease: Challenges and Opportunities · 2021
Not checked
254.
Raghu G, Berk M, Campochiaro PA, Jaeschke H, Marenzi G, Richeldi L, Wen FQ, Nicoletti F, Calverley PMA. The multifaceted therapeutic role of N-Acetylcysteine (NAC) in disorders characterized by oxidative stress. Curr Neuropharmacol. 2021;19:1202-1224.
Not in our library10.2174/1570159x19666201230144109 (opens in a new tab)
255.
Katsyuba E, Romani M, Hofer D, Auwerx J. NAD(+) homeostasis in health and disease. Nat Metab. 2020;2:9-31.
Not in our library10.1038/s42255-019-0161-5 (opens in a new tab)
256.
Chen L, Tao Y, Li J, Kang M. Pioglitazone use is associated with reduced risk of Parkinson's disease in patients with diabetes: a systematic review and meta-analysis. J Clin Neurosci. 2022;106:154-158.
Not in our library10.1016/j.jocn.2022.10.023 (opens in a new tab)
257.
Dahiya S, Tisch S, Greenfield J. The effect of GLP-1 receptor agonists in pre-clinical rodent models of Parkinson's disease: a systematic review and meta-analysis. Clin Park Relat Disord. 2022;6:100133.
Not in our library10.1016/j.prdoa.2022.100133 (opens in a new tab)
258.
The neuroprotective effects of glucagon-like peptide 1 in Alzheimer’s and Parkinson’s disease: An in-depth review · 2022
No notice
259.
Bergkvist L, Johnson ME, Mercado G, Steiner JA, Meyerdirk L, Schulz E, Madaj Z, Ma J, Becker K, Li Y, Brundin P. An extended release GLP-1 analogue increases alpha-synuclein accumulation in a mouse model of prodromal Parkinson's disease. Exp Neurol. 2021;341:113693.
Not in our library10.1016/j.expneurol.2021.113693 (opens in a new tab)
260.
Athauda D, Maclagan K, Skene SS, Bajwa-Joseph M, Letchford D, Chowdhury K, Hibbert S, Budnik N, Zampedri L, Dickson J, et al. Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390:1664-1675.
Not in our library10.1016/s0140-6736(17)31585-4 (opens in a new tab)
261.
Vijiaratnam N, Girges C, Auld G, Chau M, Maclagan K, King A, Skene S, Chowdhury K, Hibbert S, Morris H, et al. Exenatide once weekly over 2 years as a potential disease-modifying treatment for Parkinson's disease: protocol for a multicentre, randomised, double blind, parallel group, placebo controlled, phase 3 trial: the 'Exenatide-PD3' study. BMJ Open. 2021;11:e047993.
Not in our library10.1136/bmjopen-2020-047993 (opens in a new tab)
262.
Malatt C, Wu T, Bresee C, Hogg E, Wertheimer J, Tan E, Pomeroy H, Obialisi G, Tagliati M. Liraglutide improves non-motor function and activities of daily living in patients with Parkinson’s disease: a randomized, double-blind, placebo-controlled trial (P9-11.005). Neurology. 2022;98:3068.
Not in our library
263.
Dehmer T, Heneka MT, Sastre M, Dichgans J, Schulz JB. Protection by pioglitazone in the MPTP model of Parkinson's disease correlates with I kappa B alpha induction and block of NF kappa B and iNOS activation. J Neurochem. 2004;88:494-501.
Not in our library10.1046/j.1471-4159.2003.02210.x (opens in a new tab)
264.
PPARγ and PGC-1α as Therapeutic Targets in Parkinson’s · 2014
No notice
265.
Investigators. NETiPDF-Z: pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, randomised trial. Lancet Neurol. 2015;14:795-803.
Not in our library10.1016/s1474-4422(15)00144-1 (opens in a new tab)
266.
Dynamics of Dynamin-Related Protein 1 in Alzheimer’s Disease and Other Neurodegenerative Diseases · 2019
No notice
267.
Mitochondrial division inhibitor-1 is neuroprotective in the A53T-α-synuclein rat model of Parkinson’s disease · 2017
No notice
268.
Fan RZ, Guo M, Luo S, Cui M, Tieu K. Exosome release and neuropathology induced by alpha-synuclein: new insights into protective mechanisms of Drp1 inhibition. Acta Neuropathol Commun. 2019;7:184.
Not in our library10.1186/s40478-019-0821-4 (opens in a new tab)
269.
Zhang XL, Huang WM, Tang PC, Sun Y, Zhang X, Qiu L, Yu BC, Zhang XY, Hong YX, He Y, Ge XQ. Anti-inflammatory and neuroprotective effects of natural cordycepin in rotenone-induced PD models through inhibiting Drp1-mediated mitochondrial fission. Neurotoxicology. 2021;84:1-13.
Not in our library10.1016/j.neuro.2021.02.002 (opens in a new tab)
270.
Drp1 inhibition attenuates neurotoxicity and dopamine release deficits in vivo · 2014
No notice
271.
Hsieh CH, Shaltouki A, Gonzalez AE. Bettencourt da Cruz a, Burbulla LF, St Lawrence E, Schule B, Krainc D, palmer TD, Wang X: functional impairment in Miro degradation and Mitophagy is a shared feature in familial and sporadic Parkinson's disease. Cell Stem Cell. 2016;19:709-724.
Not in our library10.1016/j.stem.2016.08.002 (opens in a new tab)
272.
Shaltouki A, Hsieh CH, Kim MJ, Wang X. Alpha-synuclein delays mitophagy and targeting Miro rescues neuron loss in Parkinson's models. Acta Neuropathol. 2018;136:607-620.
Not in our library10.1007/s00401-018-1873-4 (opens in a new tab)
273.
Hsieh CH, Li L, Vanhauwaert R, Nguyen KT, Davis MD, Bu G, Wszolek ZK, Wang X. Miro1 Marks Parkinson's disease subset and Miro1 reducer rescues neuron loss in Parkinson's models. Cell Metab. 2019;30(1131–1140):e1137.
Not in our library10.1016/j.cmet.2019.08.023 (opens in a new tab)
274.
Haque ME, Thomas KJ, D'Souza C, Callaghan S, Kitada T, Slack RS, Fraser P, Cookson MR, Tandon A, Park DS. Cytoplasmic Pink1 activity protects neurons from dopaminergic neurotoxin MPTP. Proc Natl Acad Sci U S A. 2008;105:1716-1721.
Not in our library10.1073/pnas.0705363105 (opens in a new tab)
275.
Yasuda T, Hayakawa H, Nihira T, Ren YR, Nakata Y, Nagai M, Hattori N, Miyake K, Takada M, Shimada T, et al. Parkin-mediated protection of dopaminergic neurons in a chronic MPTP-minipump mouse model of Parkinson disease. J Neuropathol Exp Neurol. 2011;70:686-697.
Not in our library10.1097/nen.0b013e3182269ecd (opens in a new tab)
276.
Bian M, Liu J, Hong X, Yu M, Huang Y, Sheng Z, Fei J, Huang F. Overexpression of parkin ameliorates dopaminergic neurodegeneration induced by 1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. PLoS One. 2012;7:e39953.
Not in our library10.1371/journal.pone.0039953 (opens in a new tab)
277.
Todd AM, Staveley BE. Pink1 suppresses alpha-synuclein-induced phenotypes in a Drosophila model of Parkinson's disease. Genome. 2008;51:1040-1046.
Not in our library10.1139/g08-085 (opens in a new tab)
278.
Chung E, Choi Y, Park J, Nah W, Park J, Jung Y, Lee J, Lee H, Park S, Hwang S, et al. Intracellular delivery of Parkin rescues neurons from accumulation of damaged mitochondria and pathological alpha-synuclein. Sci Adv. 2020;6:eaba1193.
Not in our library10.1126/sciadv.aba1193 (opens in a new tab)
279.
Pinto M, Nissanka N, Peralta S, Brambilla R, Diaz F, Moraes CT. Pioglitazone ameliorates the phenotype of a novel Parkinson's disease mouse model by reducing neuroinflammation. Mol Neurodegener. 2016;11:25.
Not in our library10.1186/s13024-016-0090-7 (opens in a new tab)
280.
Yang Y, Gehrke S, Imai Y, Huang Z, Ouyang Y, Wang JW, Yang L, Beal MF, Vogel H, Lu B. Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin. Proc Natl Acad Sci U S A. 2006;103:10793-10798.
Not in our library10.1073/pnas.0602493103 (opens in a new tab)
281.
The L-type channel antagonist isradipine is neuroprotective in a mouse model of Parkinson's disease · 2011
Not checked
282.
Singh A, Verma P, Balaji G, Samantaray S, Mohanakumar KP. Nimodipine, an L-type calcium channel blocker attenuates mitochondrial dysfunctions to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice. Neurochem Int. 2016;99:221-232.
Not in our library10.1016/j.neuint.2016.07.003 (opens in a new tab)
283.
Pasternak B, Svanstrom H, Nielsen NM, Fugger L, Melbye M, Hviid A. Use of calcium channel blockers and Parkinson's disease. Am J Epidemiol. 2012;175:627-635.
Not in our library10.1093/aje/kwr362 (opens in a new tab)
284.
Tseng YF, Lin HC, Chao JC, Hsu CY, Lin HL. Calcium Channel blockers are associated with reduced risk of Parkinson's disease in patients with hypertension: a population-based retrospective cohort study. J Neurol Sci. 2021;424:117412.
Not in our library10.1016/j.jns.2021.117412 (opens in a new tab)
285.
Parkinson Study Group S-PDIIII. Isradipine versus placebo in early Parkinson disease: a randomized trial. Ann Intern Med. 2020;172:591-598.
Not in our library10.7326/m19-2534 (opens in a new tab)
286.
Surmeier DJ, Nguyen JT, Lancki N, Venuto CS, Oakes D, Simuni T, Wyse RK. Re-analysis of the STEADY-PD II trial-evidence for slowing the progression of Parkinson's disease. Mov Disord. 2022;37:334-342.
Not in our library10.1002/mds.28850 (opens in a new tab)
287.
Fereshtehnejad SM, Zeighami Y, Dagher A, Postuma RB. Clinical criteria for subtyping Parkinson's disease: biomarkers and longitudinal progression. Brain. 2017;140:1959-1976.
Not in our library10.1093/brain/awx118 (opens in a new tab)

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