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LRRK2 and neuroinflammation: partners in crime in Parkinson’s disease?

Isabella Russo, Luigi Bubacco, Elisa Greggio

Journal of Neuroinflammation · 2014 · Review

doi:10.1186/1742-2094-11-52

Abstract

It is now well established that chronic inflammation is a prominent feature of several neurodegenerative disorders including Parkinson's disease (PD). Growing evidence indicates that neuroinflammation can contribute greatly to dopaminergic neuron degeneration and progression of the disease. Recent literature highlights that leucine-rich repeat kinase 2 (LRRK2), a kinase mutated in both autosomal-dominantly inherited and sporadic PD cases, modulates inflammation in response to different pathological stimuli. In this review, we outline the state of the art of LRRK2 functions in microglia cells and in neuroinflammation. Furthermore, we discuss the potential role of LRRK2 in cytoskeleton remodeling and vesicle trafficking in microglia cells under physiological and pathological conditions. We also hypothesize that LRRK2 mutations might sensitize microglia cells toward a pro-inflammatory state, which in turn results in exacerbated inflammation with consequent neurodegeneration.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 23, 2026. Paragraph numbers are ours, so an answer can point at one.

Introduction

Leucine-rich repeat kinase 2 (LRRK2) is a large multidomain protein belonging to the family of mammalian ROCO (Ras Of COmplex) proteins, and characterized by the presence of an enzymatic core, comprising ROC/GTPase, COR (C-terminus of ROC) and serine threonine kinase domains, and by multiple protein-protein interaction domains including ankyrin and leucine-rich repeat motifs at the N-terminus, and WD40 repeats at the C-terminus. Although the physiological functions of LRRK2 are still unclear, the presence of both a GTPase and a kinase domain suggest a role in intracellular signaling, and the existence of different protein binding domains points to an additional function as a scaffolding protein for the assembly of protein complexes.

Mutations in LRRK2 cause autosomal-dominantly inherited Parkinson’s Disease, while more common variations can also act as risk factors for disease, accounting for 13% of all familial PD cases, and 1 to 2% of all sporadic PD cases. Despite intensive research efforts, little is known about the pathogenic mechanism(s) of mutant LRRK2. Interestingly, LRRK2-associated PD is clinically and pathologically similar to sporadic PD, thus indicating overlapping pathways in both familial and sporadic PD. Several mutations in LRRK2 clearly segregate with the disease, and, importantly, these mutations cluster within the two catalytic domains, suggesting that a change in enzymatic functions (GTPase and/or kinase) may mediate the pathogenic effects of LRRK2. R1441G/C/H mutations map to the ROC domain, Y1669C to the COR domain, and I2020T and G2019S mutations to the kinase domain. In this frame, the G2019S mutation is by far the most common pathogenic LRRK2 mutation, and is responsible for more than 10% of familial PD cases and 1 to 2% of sporadic PD cases. Several studies have shown that of all the LRRK2 mutations, only the G2019S mutation consistently increases kinase activity. Specifically, in vitro phosphorylation assays from independent studies showed an approximately three fold increase in kinase activity in comparison with wild-type protein, whereas ROC-COR mutations display inconsistent effects on kinase, but have significantly lower GTPase activity. Conversely, the effect of the I2020T mutation on kinase activity is less clear, with studies observing both increased and decreased activity. However, the effects of LRRK2 mutations on kinase activity have been mainly examined in vitro by monitoring autophosphorylation or phosphorylation of model peptides, making it difficult to understand the real effects of mutations on LRRK2 physiological functions. Interestingly, a recent paper by Sheng and colleagues reported that autophosphorylation on serine 1292 is a direct indicator of LRRK2 kinase activity in vivo, and that additional mutations, other than G2019S, appear to increase autophosphorylation at this site, consistent with an in vitro study focused on autophosphorylation. Monitoring phosphorylation of serine 1292 in cells represents an important tool for future studies addressing pathways and signaling networks that relate to LRRK2 kinase function.

In the brain, LRRK2, both mRNA and protein, has been detected in specific regions including the cortex, striatum, hippocampus, and with substantial lower expression, in the substantia nigra pars compacta (SNpc). LRRK2 has been reported to localize within a wide range of vesicular and membranous structures, such as mitochondria, endoplasmic reticulum, and Golgi apparatus, as well as the endolysosomal system and synaptic vesicles. Although LRRK2 protein is expressed in various brain cell types such as neurons, microglia, and astrocytes, the vast majority of studies to date have focused on investigating LRRK2 functions in neurons, being the relevant cell type that degenerates in PD. The physiological functions of LRRK2 in neuronal cells have been linked to vesicular trafficking, cytoskeletal dynamics, mitochondrial function, apoptosis, and regulation of the autophagy pathway; however, how LRRK2 mutations cause neurodegeneration in PD is currently under debate.

Effects of reactive microglia and neuroinflammation in the pathogenesis of PD

It is now well established that chronic inflammation is a prominent feature of several neurodegenerative disorders, including PD. The inflammatory response is driven by the activation of resident macrophages, local invasion of circulating immune cells, and production of cytokines, chemokines, and reactive oxygen species, all essential to recruit cells of the immune system to the compromised area. Microglia cells, the resident macrophages of the brain, constitute the first barrier of the innate immune response in the brain, and are considered to be key players during neuroinflammation. Microglia cells continually survey the microenvironment, and upon detection of abnormal changes in the surrounding tissue, they rapidly become activated, secrete inflammatory mediators, and migrate to the damaged area to eliminate pathogens or to phagocyte dead cells and/or aggregated proteins. Although a well-regulated inflammatory process is essential for tissue repair and CNS integrity, an excessive and protracted inflammatory response can turn cytotoxic, leading to significant tissue and cellular damage, thus promoting the progression of the disease.

It has been widely reported that chronic inflammation can contribute to the degeneration of dopaminergic neurons and to the progression of PD. Elevated levels of pro-inflammatory cytokines (tumour necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, and IL-6) have been found in the cerebrospinal fluid, striatum and SNpc of experimental animal models and of post-mortem brains from patients with PD. Moreover, the presence of extensive proliferation of reactive and phagocytic macrophages positive for human leukocyte antigen (HLA) has been shown around dopaminergic neurons in the SNpc of patients with PD, in animal models, and in patients with parkinsonism after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure, further indicating that microglia cells and their mediators might lead to neuronal damage and degeneration.

Microglia-mediated dopaminergic neurodegeneration is supported by numerous studies. In fact, this class of neurons exhibits a reduced antioxidant capacity and enhanced sensitivity to pro-inflammatory mediators, probably as a result of the high density of microglia cells present in SNpc compared to other brain regions. Ouchi and colleagues reported that microglia activation in the midbrain is positively correlated with dopaminergic neuronal death and motor symptom severity in the early stage of PD, supporting the notion that reactive microglia exacerbate the progression of the disease.

Supporting evidence for a direct role of inflammation in PD has recently emerged from genome-wide association studies (GWAS). Specifically, polymorphisms in genes encoding inflammatory cytokines such as TNF-α and IL-1β, and cell-surface human leukocyte antigen (HLA) are associated with a higher risk of developing PD. These genes are predominantly expressed in glial cells, and are directly involved in the inflammatory process. Although it is still controversial whether inflammation is causative or a secondary effect of earlier pathological events of PD, there is an increasing recognition of neuroinflammation as a major player in the pathology of this disease.

Remarkably, LRRK2 has been identified by GWAS as one of the susceptibility genes for leprosy and possibly for Crohn’s disease, two illnesses with a strong inflammatory component. Based on these genetic findings, a number of recent studies have explored the putative role of LRRK2 in microglia cells and the impact of LRRK2 mutations in the inflammatory response associated with PD.

What is the role of LRRK2 in microglia cells?

Microglia are highly dynamic cells with vastly branched and motile cell processes, which constantly screen the brain parenchyma, ready to detect any changes in the tissue. In response to pathological stimuli such as lipopolysaccharide (LPS), aggregated proteins, or dead neurons, microglia cells switch from a resting and ramified phenotype into an ameboid, activated phenotype. Once they have migrated toward a damaged area, they initiate a repairing program through the release of inflammatory mediators and the removal of debris by phagocytosis. A number of LRRK2 pathways have been described in neuronal cells, but here we will discuss the potential roles of this protein in the physiological and pathological functions of microglia cells.

Immune-related cellular pathways

Recent findings indicate elevated LRRK2 mRNA and protein expression in immune cells, particularly in microglia and astrocytes from human and rodent brain, and in peripheral blood mononuclear cells, mainly in B cells, dendritic cells, and macrophages. Giesert et al. investigated potential LRRK2 mRNA splice variants in brain cells; they observed that both neurons and astrocytes (but not microglia) express a transcript variant containing the alternative exon 42a, which results in a premature stop codon and a predicted protein of 2152 amino acids long. This finding is intriguing, as it suggests that LRRK2 function(s) in microglia cells may be at least partly different from those exerted in other brain cell types.

Interestingly, Moehle and colleagues observed a robust induction of LRRK2 protein in microglia cells of mouse SNpc or striatum after LPS-induced inflammation. Furthermore, in vitro studies reported increased LRRK2 protein expression in microglia cell cultures after an inflammatory stimulus induced by LPS or IFN-γ, but not after HIV-1 Tat protein-induced inflammation. In addition to increased expression levels, LRRK2 immunoprecipitated from LPS-inflamed brains was more active in in vitro autophosphorylation assays, possibly indicating that the protein is switched into an active conformation. Although the exact mechanism is not clear, two different studies reported that HIV-1 Tat protein-induced inflammation of BV2 cells or Toll-like receptor (TLR) agonists (but not TNF-α treatment of RAW264.7 macrophages) induced marked phosphorylation of LRRK2 at serines 910 and 935, a state that is possibly associated with an active LRRK2 form. Taken together, these data suggest that LRRK2 expression and enzymatic activity are required during an inflammatory response; however, the specific pathways and signaling cascades that LRRK2 orchestrates have not been characterized.

Additional studies further support a role for LRRK2 as regulator of inflammation. Murine microglia cells with inhibited or down-regulated LRRK2 showed attenuated levels of LPS-induced inflammatory mediators at the mRNA and protein level, including TNF-α, IL-1β, IL-6 and inducible nitric oxide synthase (iNOS). In particular, LRRK2 knockdown microglia exhibited a significant reduction of nuclear factor kappa B (NF-κB) transcriptional activity following TLR-mediated immune signaling induced by LPS, and an increase of DNA-binding activity of the NF-κB p50 inhibitor subunit. As NF-κB activity is essential for induction of pro-inflammatory cytokines, LRRK2 might control its activation and the consequent transcription of pro-inflammatory mediators, through a yet undisclosed mechanism. In another study, Liu and colleagues demonstrated that LRRK2 can function as negative regulator of nuclear factor of activated T cells (NFAT) transcription factors, a class of molecules implicated in the inflammatory response in a large set of immune cells. In particular, they observed that LRRK2 inhibits NFAT nuclear translocation in a TLR-independent manner, and thus inhibits the transcription of immune response genes via interaction with the NRON (noncoding (RNA) repressor of NFAT) complex in immune peripheral cells. Although a significant amount of progress has been made, how LRRK2 modulates transcription factors and induction of inflammatory genes remains controversial and needs to be carefully explored.

Notably, Gillardon and colleagues observed that LPS-activated microglia cells from LRRK2 R1441G knock-in mice exhibited increased expression and secretion of pro-inflammatory cytokines and reduced expression of anti-inflammatory cytokines compared with wild-type control microglia cells. Interestingly, gene expression profiling of LRRK2 R1441G microglia cells under unstimulated conditions revealed that several cytokines, chemokines, and membrane receptors regulating microglia activation were significantly increased compared with wild-type cells, indicative of a basal sensitization toward a pro-inflammatory phenotype. In addition, conditioned medium from LPS-stimulated LRRK2 R1441G microglia added to primary cortical neurons caused increased neuronal death compared with medium from wild-type LRRK2 microglia. Overall, these data indicate that LRRK2 is involved in the cellular pathways induced by inflammation, and that LRRK2 R1441G mutation might push microglia toward a pro-inflammatory state, which results, in turn, in exacerbated inflammation and consequent neurodegeneration in patients with PD (Figure 1).

Of note, Lopez de Maturana and colleagues recently reported the effects of pro-inflammatory LPS stimulus on epidermal cells from patients with PD who carried R1441G or G2019S LRRK2 mutations, and patients with idiopathic PD compared with controls. Interestingly, these authors found that patient cells had a blunted response to LPS compared with control cells. However, whether immune cells respond to LPS priming in a similar manner remains to be determined.

Cytoskeleton reorganization

LRRK2 has been suggested to influence actin cytoskeleton and microtubule dynamics, and these functions might be implicated in the neuronal damage underlying PD. Various studies have reported the involvement of LRRK2 kinase activity in neurite outgrowth and maintenance of neuronal processes. There seems to be general agreement that the LRRK2 G2019S mutation has an inhibitory effect on neurite outgrowth and branching. In this context, Parisiadou and colleagues hypothesized that the G2019S mutation causes increased actin polymerization and ERM (ezrin, radixin, moesin) protein phosphorylation in neuronal filopodia, thus acting as a physical barrier that prevents the extensions of microtubule and leads, in turn, to inhibition of neuronal processes. These observations find a link with the proposed function of LRRK2 in the context of the microtubule network. In particular, it was reported that LRRK2 interacts through its ROC/GTPase domain and phosphorylates neuronal β-tubulin both in vitro and in vivo, as demonstrated by reduced phosphorylation of β-tubulin immunoprecipitated from knockout compared with wild-type mouse brains. Furthermore, in vitro LRRK2 enhances tubulin polymerization in the presence of microtubule-associated proteins, and phosphorylates tubulin-associated Tau, whereas in vivo, Tau is hyperphosphorylated in brains from R1441G trangenic mice. Taken together, these data indicate that LRRK2 regulates the organization of the actin cytoskeleton and microtubule assembly.

Cytoskeleton reorganization is also a critical step for brain macrophage functions. Indeed, the rapid changes in cell morphology and cell activity that microglia cells undertake upon activation are governed by microtubules and by actin cytoskeleton remodeling. Even microglia motility is a process that results from coordinated changes in the actin cytoskeleton and in the formation of cell-substrate adhesion sites. The actin cytoskeleton provides the driving force at the cell front, while the microtubule network regulates the rear retraction. During migration, microglia cells exhibit long, thin extensions called filopodia, which are supported by tight and dynamic bundles of actin filaments that continuously polymerize and depolymerize to support the cell movement.

Supporting a role of LRRK2 in cytoskeleton reorganization during microglia activation, two recent studies reported that inflammatory stimuli failed to induce significant morphological changes of fine process extensions and cytoskeleton remodeling in LRRK2 knockdown or LRRK2 inhibitor-treated microglia cells. Moreover, Moehle and colleagues observed in vitro that LRRK2 inhibition prevents microglial migration in response to ADP, a potent microglial chemoattractant. Another study demonstrated that human LRRK2 G2019S and mouse LRRK2 knockout fibroblasts exhibit altered cell migration in culture, with LRRK2 G2019S fibroblasts migrating faster and LRRK2 knockout migrating slower compared with control cells. As the G2019S mutation increases LRRK2 catalytic function, LRRK2 kinase activity appears to be required for cytoskeleton remodeling and for motility of microglia cells.

Microglia are the predominant phagocytes in the brain. They act as a surveillance system for microbes and pathological proteins, and remove apoptotic cells and cellular debris in the brain. They engulf and digest microbes or pathological proteins by binding to them via specialized surface receptors (such as TLRs) and subsequently trapping them into a phagosome, which then fuses with a lysosome to be digested. Phagocytosis induces dramatic changes in the shape and the movement of a cell, including extension of the membrane and actin filaments, through reorganization of the cytoskeleton. Barcia and colleagues demonstrated using in vivo high-resolution imaging that the entire microglia cell body is involved in the formation of a phagocytic cup. Moreover, imaging of fluorescent actin molecules during phagocytosis showed coordinated movement of the cytoskeleton in the cup, which is mediated by a combination of localized actin polymerization and depolymerization, together with the contraction of actin filament networks. Interestingly, Marker et al. showed that LRRK2 might be involved in microglia phagocytosis. They found that pharmacological inhibition of LRRK2 attenuated microglial phagocytosis of fluorescent beads after an inflammatory stimulus. In addition, BV2-immortalized microglia cells co-cultured in the axonal compartment of primary neurons (to study phagocytosis of neuronal processes in the absence of cell bodies), and exposed to inflammatory conditions, completely phagocytosed and destroyed axonal arbors. By contrast, treatment of co-cultures with the LRRK2 inibitor IN-1 protected the axons and neuronal phagocytosis by clearing microglia.

Overall, these data suggest that LRRK2 regulates microglia activation, migration, and phagocytosis, although the molecular mechanisms underlying these processes are still unknown. One possibility is that LRRK2 orchestrates cytoskeletal components such as actin, tubulin. and ERM proteins, and that the pathological G2019S mutation causes hyperphosphorylation and hyperpolymerization of cytoskeleton components, which leads, in turn, to reactive microglia with enhanced cell activity, migration, and phagocytosis in response to pathological stimuli, thus contributing to the pathogenesis of PD (Figure 1).

Vesicle trafficking

Strong evidence supports a role for LRRK2 in the secretory and endocytic pathways. Multiple in vivo and in vitro studies have reported that LRRK2 overexpression or knockdown affects synaptic vesicle endocytosis and exocytosis. In detail, LRRK2 modulates synaptic vesicle trafficking by interaction with pre-synaptic proteins such as actin, syntaxin, synaptic vesicle glycoprotein 2A (SV2A), N-ethylmaleimide-sensitive factor (NSF), and Synapsin I; affects synaptic vesicles endocytosis through interaction with Rab5b and EndoA, critical components of the endocytic machinery; and regulates the numbers of readily releasable vesicles and their release in hippocampal neurons by interaction and phosphorylation of Snapin protein. Importantly, the G2019S and R1441G mutations were shown to increase the levels of dopamine receptor D1 on the membrane surface, supporting the notion that pathological LRRK2 activity might affect vesicle trafficking and release.

LRRK2 has also been reported to regulate the endocytic pathway involved in the autophagic-lysosomal process, an important clearance route for several aggregated or unfolded proteins. Interestingly, the LRRK2 Drosophila homolog interacts with Rab7, modulating the degradation of autophagosomes. Human LRRK2 forms a complex with Rab7L1, an important component of the autophagic-lysosomal pathway. In addition, LRRK2 interacting with Rab5 might also affect the early step of autophagosome formation.

Vesicle trafficking in secretory and endocytic pathways are well described in microglia cells during cytokine release, delivery of membrane receptors to the cell membrane, and phagocytosis. Transport of inflammation-induced cytokines (such as TNF-α and IL-6) from the endoplasmic reticulum to the cell surface occurs through the endosomal system, and relies on a complex array of trafficking machinery to ensure the accurate docking and fusion of carrier vesicles to their designated target membranes. Delivery and internalization of membrane receptors in macrophages are essential for the regulation of cell activation, and their trafficking also occurs through endosomes. Notably, Rab7 is fundamental for the trafficking of receptor-containing vesicles involved in the inflammatory response, thus supporting the notion that LRRK2 might affect the expression of membrane receptors on microglia cells.

The endosomal pathway also plays a central role during phagocytosis. Macrophages, when in contact with pathogens or dying cells, initiate a sequence of membrane fusion events that culminate with the formation of a phagocytic cup, which is followed by the formation of a nascent phagosome around the ingested material, and its consequent internalization. The phagosome is then reshaped to form the phagolysosome, where pathogens are degraded to produce antigenic peptides. Multiple soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are required for the formation and the maturation of phagosome. Specifically, phagocytic cup formation is determined by fusion of the plasma membrane with intracellular organelles including recycling endosomes, late endosomes, and endoplasmic reticulum, which have a large amount of membrane and contain the appropriate SNARE and Rab GTPase proteins. It has been demonstrated that macrophages, when activated, regulate the expression of SNAREs and GTPases to provide a large set of proteins for membrane fusion, important for phagocytic cup formation.

Although a role for LRRK2 in vesicle trafficking in microglia cells has not been described, we speculate that LRRK2 activity may be important for the release of inflammatory mediators, delivery of membrane receptors, and phagocytotic processes. In particular, LRRK2 might regulate the components of the fusion machinery, such as its partner NSF or Rab GTPase proteins, which have been shown to contribute to the fusion of vesicles containing inflammatory mediators, receptors, and pathogens to be eliminated. It should be noted that several receptors regulating microglial activation, such as major histocompatibility complex (MHC) class II and CD11b, which have also been observed to be up-regulated in brains of patients with PD, showed increased mRNA expression under basal conditions in transgenic microglia with LRRK2 R1441G mutation, thus suggesting that LRRK2 might affect the expression of these receptors. Moreover, when these cells were activated with LPS, the levels of cytokines/chemokines, proteins, and mRNAs massively increased compared with wild-type cultures, thus indicating that LRRK2 might play a key role in vesicle trafficking and release in microglia cells and might be important in switching these cells toward a pro-inflammatory phenotype (Figure 1).

Conclusions

Recent literature indicates that microglial LRRK2 plays a role in the cellular pathways induced by inflammatory stimuli. Based on its complex architecture with different functional domains, LRRK2 might be involved in more than one cellular process. Although a number of studies have analyzed the effects of LRRK2 kinase activity using different microglia-related readouts, such as morphological changes and inflammatory mediator release, evidence on how LRRK2 might affect these processes is currently lacking. Here we hypothesize that abnormal LRRK2 kinase activity, due to the presence of LRRK2 mutations, might modulate the phenotype of microglia through hyperpolymerization and hyperphosphorylation of cytoskeleton and vesicle components, thus pushing these cells toward a pro-inflammatory state. In this regard, Gillardon and colleagues observed that the LRRK2 R1441G mutation sensitizes microglia cells toward a neurotoxic state. Similar to G2019S, the R1441G mutation causes an approximately 2.5-fold increase of serine 1292 autophosphorylation in cells overexpressing LRRK2-R1441G compared with wild-type LRRK2, supporting the notion that the increased kinase activity of LRRK2 may push microglia toward a pro-inflammatory phenotype. One possibility is that the R1441G mutation increases kinase activity through its reduced GTP hydrolysis activity, although the cross-talk between GTPase and the kinase domain is currently unclear.

The identification of microglia-specific kinase substrates, GTPase downstream effectors, and interactors, will provide valuable insight into the emerging function of LRRK2 in the regulation of neuroinflammation, with the potential of uncovering new molecular mechanisms underlying the pathogenesis of PD, and consequently novel targets for drug treatments.

Abbreviations

CNS: Central nervous system; COR: C-terminus of ROC; ERM: ezrin, radixin, moesin; GWAS: Genome-wide association study; HLA: Human leukocyte antigen; iNOS: Inducible nitric oxide synthase; IFN: Interferon; IL: Interleukin; LPS: Lipopolysaccharide; LRRK2: Leucine-rich repeat kinase 2; MHC: Major histocompatibility complex; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NFAT: nuclear factor of activated T cells; NF-κB: nuclear factor kappa B; NRON: Noncoding (RNA) repressor of nuclear factor of activated T cells; NSF: N-ethylmaleimide-sensitive factor; PD: Parkinson’s disease; ROC: Ras of complex proteins; SNARE: Soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SNpc: Substantia nigra pars compacta; SV2A: Synaptic vesicle glycoprotein 2A; TNF: Tumor necrosis factor; TLR: Toll-like receptor.

Competing interests

The authors declare that they have no competing interest.

Authors’ contributions

IR and EG conceived the paper; IR, LB, and EG wrote the paper. All authors read and approved the final manuscript.

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    Giesert F Hofmann A Burger A Zerle J Kloos K Hafen U Ernst L Zhang J Vogt-Weisenhorn DM Wurst W Expression analysis of Lrrk1, Lrrk2 and Lrrk2 splice variants in micePLoS One2013 8e63778

    Not in our library10.1371/journal.pone.0063778

  27. 27.

    Dodson MW Zhang T Jiang C Chen S Guo M Roles of the Drosophila LRRK2 homolog in Rab7-dependent lysosomal positioningHum Mol Genet2012 2113501363

    Not in our library10.1093/hmg/ddr573

  28. 28.

    Alegre-Abarrategui J Christian H Lufino MM Mutihac R Venda LL Ansorge O Wade-Martins R LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular modelHum Mol Genet2009 1840224034

    Not in our library10.1093/hmg/ddp346

  29. 29.

    Belluzzi E Greggio E Piccoli G Presynaptic dysfunction in Parkinson’s disease: a focus on LRRK2Biochem Soc Trans2012 4011111116

    Not in our library10.1042/bst20120124

  30. 30.

    Moehle MS Webber PJ Tse T Sukar N Standaert DG DeSilva TM Cowell RM West AB LRRK2 inhibition attenuates microglial inflammatory responsesJ Neurosci2012 3216021611

    Not in our library10.1523/jneurosci.5601-11.2012

  31. 31.

    Piccoli G Condliffe SB Bauer M Giesert F Boldt K De Astis S Meixner A Sarioglu H Vogt-Weisenhorn DM Wurst W Gloeckner CJ Matteoli M Sala C Ueffing M LRRK2 controls synaptic vesicle storage and mobilization within the recycling poolJ Neurosci2011 3122252237

    Not in our library10.1523/jneurosci.3730-10.2011

  32. 32.

    Matta S Van Kolen K da Cunha R van den Bogaart G Mandemakers W Miskiewicz K De Bock PJ Morais VA Vilain S Haddad D Delbroek L Swerts J Chávez-Gutiérrez L Esposito G Daneels G Karran E Holt M Gevaert K Moechars DW De Strooper B Verstreken P LRRK2 controls an EndoA phosphorylation cycle in synaptic endocytosisNeuron2012 7510081021

    Not in our library10.1016/j.neuron.2012.08.022

  33. 33.

    Kett LR Boassa D Ho CC Rideout HJ Hu J Terada M Ellisman M Dauer WT LRRK2 Parkinson disease mutations enhance its microtubule associationHum Mol Genet2012 21890899

    Not in our library10.1093/hmg/ddr526

  34. 34.
    A Direct Interaction between Leucine-rich Repeat Kinase 2 and Specific β-Tubulin Isoforms Regulates Tubulin Acetylation · 2014
    No notice
  35. 35.

    Papkovskaia TD Chau KY Inesta-Vaquera F Papkovsky DB Healy DG Nishio K Staddon J Duchen MR Hardy J Schapira AH Cooper JM G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarizationHum Mol Genet2012 2142014213

    Not in our library10.1093/hmg/dds244

  36. 36.

    Wang X Yan MH Fujioka H Liu J Wilson-Delfosse A Chen SG Perry G Casadesus G Zhu X LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1Hum Mol Genet2012 2119311944

    Not in our library10.1093/hmg/dds003

  37. 37.

    Ho CC Rideout HJ Ribe E Troy CM Dauer WT The Parkinson disease protein leucine-rich repeat kinase 2 transduces death signals via Fas-associated protein with death domain and caspase-8 in a cellular model of neurodegenerationJ Neurosci2009 2910111016

    Not in our library10.1523/jneurosci.5175-08.2009

  38. 38.

    Plowey ED Cherra SJ 3rd Liu YJ Chu CT Role of autophagy in G2019S-LRRK2-associated neurite shortening in differentiated SH-SY5Y cellsJ Neurochem2008 10510481056

    Not in our library10.1111/j.1471-4159.2008.05217.x

  39. 39.

    Gomez-Suaga P Luzon-Toro B Churamani D Zhang L Bloor-Young D Patel S Woodman PG Churchill GC Hilfiker S Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADPHum Mol Genet2012 21511525

    Not in our library10.1093/hmg/ddr481

  40. 40.
    Inhibition of LRRK2 kinase activity stimulates macroautophagy · 2013
    No notice
  41. 41.

    Orenstein SJ Kuo SH Tasset I Arias E Koga H Fernandez-Carasa I Cortes E Honig LS Dauer W Consiglio A Raya A Sulzer D Cuervo AM Interplay of LRRK2 with chaperone-mediated autophagyNat Neurosci2013 16394406

    Not in our library10.1038/nn.3350

  42. 42.

    Russo I Barlati S Bosetti F Effects of neuroinflammation on the regenerative capacity of brain stem cellsJ Neurochem2011 116947956

    Not in our library10.1111/j.1471-4159.2010.07168.x

  43. 43.

    Pradhan S Andreasson K Commentary: progressive inflammation as a contributing factor to early development of Parkinson’s diseaseExp Neurol2013 241148155

    Not in our library10.1016/j.expneurol.2012.12.008

  44. 44.

    Russo I Amornphimoltham P Weigert R Barlati S Bosetti F Cyclooxygenase-1 is involved in the inhibition of hippocampal neurogenesis after lipopolysaccharide-induced neuroinflammationCell Cycle2011 1025682573

    Not in our library10.4161/cc.10.15.15946

  45. 45.

    Russo I Caracciolo L Tweedie D Choi SH Greig NH Barlati S Bosetti F 3,6′-Dithiothalidomide, a new TNF-alpha synthesis inhibitor, attenuates the effect of Abeta1-42 intracerebroventricular injection on hippocampal neurogenesis and memory deficitJ Neurochem2012 12211811192

    Not in our library10.1111/j.1471-4159.2012.07846.x

  46. 46.

    Neumann H Kotter MR Franklin RJ Debris clearance by microglia: an essential link between degeneration and regenerationBrain2009 132288295

    Not in our library10.1093/brain/awn109

  47. 47.

    Nimmerjahn A Kirchhoff F Helmchen F Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivoScience2005 30813141318

    Not in our library10.1126/science.1110647

  48. 48.

    Gao HM Hong JS Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progressionTrends Immunol2008 29357365

    Not in our library10.1016/j.it.2008.05.002

  49. 49.

    Hirsch EC Hunot S Neuroinflammation in Parkinson’s disease: a target for neuroprotection?Lancet Neurol2009 8382397

    Not in our library10.1016/s1474-4422(09)70062-6

  50. 50.

    Mogi M Harada M Riederer P Narabayashi H Fujita K Nagatsu T Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patientsNeurosci Lett1994 165208210

    Not in our library10.1016/0304-3940(94)90746-3

  51. 51.

    McGeer PL Itagaki S Boyes BE McGeer EG Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brainsNeurology1988 3812851291

    Not in our library10.1212/wnl.38.8.1285

  52. 52.

    Hurley SD O’Banion MK Song DD Arana FS Olschowka JA Haber SN Microglial response is poorly correlated with neurodegeneration following chronic, low-dose MPTP administration in monkeysExp Neurol2003 184659668

    Not in our library10.1016/s0014-4886(03)00273-5

  53. 53.

    Langston JW Forno LS Tetrud J Reeves AG Kaplan JA Karluk D Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposureAnn Neurol1999 46598605

    Not in our library10.1002/1531-8249(199910)46:4<598::aid-ana7>3.0.co;2-f

  54. 54.

    Sriram K Miller DB O’Callaghan JP Minocycline attenuates microglial activation but fails to mitigate striatal dopaminergic neurotoxicity: role of tumor necrosis factor-alphaJ Neurochem2006 96706718

    Not in our library10.1111/j.1471-4159.2005.03566.x

  55. 55.

    Aloisi F Immune function of microgliaGlia2001 36165179

    Not in our library10.1002/glia.1106

  56. 56.

    Jenner P Olanow CW Understanding cell death in Parkinson’s diseaseAnn Neurol1998 44S72S84

    Not in our library10.1002/ana.410440712

  57. 57.

    Whitton PS Inflammation as a causative factor in the aetiology of Parkinson’s diseaseBr J Pharmacol2007 150963976

    Not in our library10.1038/sj.bjp.0707167

  58. 58.

    Tansey MG Goldberg MS Neuroinflammation in Parkinson’s disease: its role in neuronal death and implications for therapeutic interventionNeurobiol Dis2010 37510518

    Not in our library10.1016/j.nbd.2009.11.004

  59. 59.

    Russo I Bubacco L Greggio E Exosomes-associated neurodegeneration and progression of Parkinson’s diseaseAm J Neurodegener Dis2012 1217225

    Not in our library

  60. 60.

    Ouchi Y Yagi S Yokokura M Sakamoto M Neuroinflammation in the living brain of Parkinson’s diseaseParkinsonism Relat Disord2009 15Suppl 3S200S204

    Not in our library10.1016/s1353-8020(09)70814-4

  61. 61.

    Hamza TH Zabetian CP Tenesa A Laederach A Montimurro J Yearout D Kay DM Doheny KF Paschall J Pugh E Kusel VI Collura R Roberts J Griffith A Samii A Scott WK Nutt J Factor SA Payami H Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s diseaseNat Genet2010 42781785

    Not in our library10.1038/ng.642

  62. 62.

    Ahmed I Tamouza R Delord M Krishnamoorthy R Tzourio C Mulot C Nacfer M Lambert JC Beaune P Laurent-Puig P Loriot MA Charron D Elbaz A Association between Parkinson’s disease and the HLA-DRB1 locusMov Disord2012 2711041110

    Not in our library10.1002/mds.25035

  63. 63.

    Bialecka M Klodowska-Duda G Kurzawski M Slawek J Gorzkowska A Opala G Bialecki P Sagan L Drozdzik M Interleukin-10 (IL10) and tumor necrosis factor alpha (TNF) gene polymorphisms in Parkinson’s disease patientsParkinsonism Relat Disord2008 14636640

    Not in our library10.1016/j.parkreldis.2008.02.001

  64. 64.

    Wahner AD Sinsheimer JS Bronstein JM Ritz B Inflammatory cytokine gene polymorphisms and increased risk of Parkinson diseaseArch Neurol2007 64836840

    Not in our library10.1001/archneur.64.6.836

  65. 65.

    Chung CY Seo H Sonntag KC Brooks A Lin L Isacson O Cell type-specific gene expression of midbrain dopaminergic neurons reveals molecules involved in their vulnerability and protectionHum Mol Genet2005 1417091725

    Not in our library10.1093/hmg/ddi178

  66. 66.

    Zhang FR Huang W Chen SM Sun LD Liu H Li Y Cui Y Yan XX Yang HT Yang RD Chu TS Zhang C Zhang L Han JW Yu GQ Quan C Yu YX Zhang Z Shi BQ Zhang LH Cheng H Wang CY Lin Y Zheng HF Fu XA Zuo XB Wang Q Long H Sun YP Cheng YL Genomewide association study of leprosyN Engl J Med2009 36126092618

    Not in our library10.1056/nejmoa0903753

  67. 67.

    Umeno J Asano K Matsushita T Matsumoto T Kiyohara Y Iida M Nakamura Y Kamatani N Kubo M Meta-analysis of published studies identified eight additional common susceptibility loci for Crohn’s disease and ulcerative colitisInflamm Bowel Dis2011 1724072415

    Not in our library10.1002/ibd.21651

  68. 68.

    Barrett JC Hansoul S Nicolae DL Cho JH Duerr RH Rioux JD Brant SR Silverberg MS Taylor KD Barmada MM Bitton A Dassopoulos T Datta LW Green T Griffiths AM Kistner EO Murtha MT Regueiro MD Rotter JI Schumm LP Steinhart AH Targan SR Xavier RJ Libioulle C Sandor C Lathrop M Belaiche J Dewit O Gut I NIDDK IBD Genetics ConsortiumGenome-wide association defines more than 30 distinct susceptibility loci for Crohn’s diseaseNat Genet2008 40955962

    Not in our library10.1038/ng.175

  69. 69.

    Ohsawa K Kohsaka S Dynamic motility of microglia: purinergic modulation of microglial movement in the normal and pathological brainGlia2011 5917931799

    Not in our library10.1002/glia.21238

  70. 70.

    Garden GA Moller T Microglia biology in health and diseaseJ Neuroimmune Pharmacol2006 1127137

    Not in our library10.1007/s11481-006-9015-5

  71. 71.

    Abd-El-Basset EM Abd-El-Barr MM Effect of interleukin-1beta on the expression of actin isoforms in cultured mouse astrogliaAnat Rec (Hoboken)2011 2941623

    Not in our library10.1002/ar.21303

  72. 72.

    Cookson MR The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson’s diseaseNat Rev Neurosci2010 11791797

    Not in our library10.1038/nrn2935

  73. 73.

    Parisiadou L Cai H LRRK2 function on actin and microtubule dynamics in Parkinson diseaseCommun Integr Biol2010 3396400

    Not in our library10.4161/cib.3.5.12286

  74. 74.

    Berwick DC Harvey K LRRK2 signaling pathways: the key to unlocking neurodegeneration?Trends Cell Biol2011 21257265

    Not in our library10.1016/j.tcb.2011.01.001

  75. 75.

    Miklossy J Arai T Guo JP Klegeris A Yu S McGeer EG McGeer PL LRRK2 expression in normal and pathologic human brain and in human cell linesJ Neuropathol Exp Neurol2006 65953963

    Not in our library10.1097/01.jnen.0000235121.98052.54

  76. 76.

    Marker DF Puccini JM Mockus TE Barbieri J Lu SM Gelbard HA LRRK2 kinase inhibition prevents pathological microglial phagocytosis in response to HIV-1 Tat proteinJ Neuroinflammation2012 9261

    Not in our library10.1186/1742-2094-9-261

  77. 77.

    Hakimi M Selvanantham T Swinton E Padmore RF Tong Y Kabbach G Venderova K Girardin SE Bulman DE Scherzer CR LaVoie MJ Gris D Park DS Angel JB Shen J Philpott DJ Schlossmacher MG Parkinson’s disease-linked LRRK2 is expressed in circulating and tissue immune cells and upregulated following recognition of microbial structuresJ Neural Transm2011 118795808

    Not in our library10.1007/s00702-011-0653-2

  78. 78.
    Regulation of LRRK2 Expression Points to a Functional Role in Human Monocyte Maturation · 2011
    No notice
  79. 79.

    Gillardon F Schmid R Draheim H Parkinson’s disease-linked leucine-rich repeat kinase 2(R1441G) mutation increases proinflammatory cytokine release from activated primary microglial cells and resultant neurotoxicityNeuroscience2012 2084148

    Not in our library10.1016/j.neuroscience.2012.02.001

  80. 80.
    The IkappaB Kinase Family Phosphorylates the Parkinson’s Disease Kinase LRRK2 at Ser935 and Ser910 during Toll-Like Receptor Signaling · 2012
    Expression of concern
  81. 81.
    Impaired Inflammatory Responses in Murine Lrrk2-Knockdown Brain Microglia · 2012
    No notice
  82. 82.

    Choi SH Langenbach R Bosetti F Genetic deletion or pharmacological inhibition of cyclooxygenase-1 attenuate lipopolysaccharide-induced inflammatory response and brain injuryFASEB J2008 2214911501

    Not in our library10.1096/fj.07-9411com

  83. 83.

    Lee M Neurotransmitters and microglial-mediated neuroinflammationCurr Protein Pept Sci2013 142132

    Not in our library10.2174/1389203711314010005

  84. 84.

    Mogi M Togari A Kondo T Mizuno Y Komure O Kuno S Ichinose H Nagatsu T Caspase activities and tumor necrosis factor receptor R1 (p55) level are elevated in the substantia nigra from parkinsonian brainJ Neural Transm2000 107335341

    Not in our library10.1007/s007020050028

  85. 85.

    Liu Z Lee J Krummey S Lu W Cai H Lenardo MJ The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel diseaseNat Immunol2011 1210631070

    Not in our library10.1038/ni.2113

  86. 86.

    de Maturana LR Aguila JC Sousa A Vazquez N Del Rio P Aiastui A Gorostidi A de Munain LA Sanchez-Pernaute R Leucine-rich repeat kinase 2 modulates cyclooxygenase 2 and the inflammatory response in idiopathic and genetic Parkinson’s diseaseNeurobiol Aging2014 511161124

    Not in our library10.1016/j.neurobiolaging.2013.11.018

  87. 87.

    Caesar M Zach S Carlson CB Brockmann K Gasser T Gillardon F Leucine-rich repeat kinase 2 functionally interacts with microtubules and kinase-dependently modulates cell migrationNeurobiol Dis2013 54280288

    Not in our library10.1016/j.nbd.2012.12.019

  88. 88.

    Meixner A Boldt K Van Troys M Askenazi M Gloeckner CJ Bauer M Marto JA Ampe C Kinkl N Ueffing M A QUICK screen for Lrrk2 interaction partners–leucine-rich repeat kinase 2 is involved in actin cytoskeleton dynamicsMol Cell Proteomics2011 10M110 001172

    Not in our library10.1074/mcp.m110.001172

  89. 89.

    Gillardon F Leucine-rich repeat kinase 2 phosphorylates brain tubulin-beta isoforms and modulates microtubule stability–a point of convergence in parkinsonian neurodegeneration?J Neurochem2009 11015141522

    Not in our library10.1111/j.1471-4159.2009.06235.x

  90. 90.

    MacLeod D Dowman J Hammond R Leete T Inoue K Abeliovich A The familial Parkinsonism gene LRRK2 regulates neurite process morphologyNeuron2006 52587593

    Not in our library10.1016/j.neuron.2006.10.008

  91. 91.

    Parisiadou L Xie C Cho HJ Lin X Gu XL Long CX Lobbestael E Baekelandt V Taymans JM Sun L Cai H Phosphorylation of ezrin/radixin/moesin proteins by LRRK2 promotes the rearrangement of actin cytoskeleton in neuronal morphogenesisJ Neurosci2009 291397113980

    Not in our library10.1523/jneurosci.3799-09.2009

  92. 92.

    Sepulveda B Mesias R Li X Yue Z Benson DL Short- and long-term effects of LRRK2 on axon and dendrite growthPLoS One2013 8e61986

    Not in our library10.1371/journal.pone.0061986

  93. 93.

    Gandhi PN Wang X Zhu X Chen SG Wilson-Delfosse AL The Roc domain of leucine-rich repeat kinase 2 is sufficient for interaction with microtubulesJ Neurosci Res2008 8617111720

    Not in our library10.1002/jnr.21622

  94. 94.

    Lin X Parisiadou L Gu XL Wang L Shim H Sun L Xie C Long CX Yang WJ Ding J Chen ZZ Gallant PE Tao-Cheng JH Rudow G Troncoso JC Liu Z Li Z Cai H Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson’s-disease-related mutant alpha-synucleinNeuron2009 64807827

    Not in our library10.1016/j.neuron.2009.11.006

  95. 95.

    Kawakami F Yabata T Ohta E Maekawa T Shimada N Suzuki M Maruyama H Ichikawa T Obata F LRRK2 phosphorylates tubulin-associated tau but not the free molecule: LRRK2-mediated regulation of the tau-tubulin association and neurite outgrowthPLoS One2012 7e30834

    Not in our library10.1371/journal.pone.0030834

  96. 96.

    Li Y Liu W Oo TF Wang L Tang Y Jackson-Lewis V Zhou C Geghman K Bogdanov M Przedborski S Beal MF Burke RE Li C Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson’s diseaseNat Neurosci2009 12826828

    Not in our library10.1038/nn.2349

  97. 97.

    Wehrle-Haller B Imhof BA Actin, microtubules and focal adhesion dynamics during cell migrationInt J Biochem Cell Biol2003 353950

    Not in our library10.1016/s1357-2725(02)00071-7

  98. 98.

    Stuart LM Bell SA Stewart CR Silver JM Richard J Goss JL Tseng AA Zhang A El Khoury JB Moore KJ CD36 signals to the actin cytoskeleton and regulates microglial migration via a p130Cas complexJ Biol Chem2007 2822739227401

    Not in our library10.1074/jbc.m702887200

  99. 99.

    Gardel ML Schneider IC Aratyn-Schaus Y Waterman CM Mechanical integration of actin and adhesion dynamics in cell migrationAnnu Rev Cell Dev Biol2010 26315333

    Not in our library10.1146/annurev.cellbio.011209.122036

  100. 100.

    Small JV Stradal T Vignal E Rottner K The lamellipodium: where motility beginsTrends Cell Biol2002 12112120

    Not in our library10.1016/s0962-8924(01)02237-1

  101. 101.

    Holmes KC Popp D Gebhard W Kabsch W Atomic model of the actin filamentNature1990 3474449

    Not in our library10.1038/347044a0

  102. 102.

    Cross AK Woodroofe MN Chemokines induce migration and changes in actin polymerization in adult rat brain microglia and a human fetal microglial cell line in vitroJ Neurosci Res1999 551723

    Not in our library10.1002/(sici)1097-4547(19990101)55:1<17::aid-jnr3>3.0.co;2-j

  103. 103.

    Welch MD Mullins RD Cellular control of actin nucleationAnnu Rev Cell Dev Biol2002 18247288

    Not in our library10.1146/annurev.cellbio.18.040202.112133

  104. 104.

    Faff L Nolte C Extracellular acidification decreases the basal motility of cultured mouse microglia via the rearrangement of the actin cytoskeletonBrain Res2000 8532231

    Not in our library10.1016/s0006-8993(99)02221-0

  105. 105.

    Swanson JA Shaping cups into phagosomes and macropinosomesNat Rev Mol Cell Biol2008 9639649

    Not in our library10.1038/nrm2447

  106. 106.

    Castellano F Chavrier P Caron E Actin dynamics during phagocytosisSemin Immunol2001 13347355

    Not in our library10.1006/smim.2001.0331

  107. 107.

    Barcia C Ros CM Annese V Carrillo-de Sauvage MA Ros-Bernal F Gomez A Yuste JE Campuzano CM de Pablos V Fernandez-Villalba E Herrero MT ROCK/Cdc42-mediated microglial motility and gliapse formation lead to phagocytosis of degenerating dopaminergic neurons in vivoSci Rep2012 2809

    Not in our library10.1038/srep00809

  108. 108.

    Swanson JA Johnson MT Beningo K Post P Mooseker M Araki N A contractile activity that closes phagosomes in macrophagesJ Cell Sci1999 112Pt 3307316

    Not in our library10.1242/jcs.112.3.307

  109. 109.
    GTPase Activity Plays a Key Role in the Pathobiology of LRRK2 · 2010
    No notice
  110. 110.

    Shin N Jeong H Kwon J Heo HY Kwon JJ Yun HJ Kim CH Han BS Tong Y Shen J Hatano T Hattori N Kim KS Chang S Seol W LRRK2 regulates synaptic vesicle endocytosisExp Cell Res2008 31420552065

    Not in our library10.1016/j.yexcr.2008.02.015

  111. 111.

    Yun HJ Park J Ho DH Kim H Kim CH Oh H Ga I Seo H Chang S Son I Seol W LRRK2 phosphorylates Snapin and inhibits interaction of Snapin with SNAP-25Exp Mol Med2013 45e36

    Not in our library10.1038/emm.2013.68

  112. 112.

    Migheli R Del Giudice MG Spissu Y Sanna G Xiong Y Dawson TM Dawson VL Galioto M Rocchitta G Biosa A Serra PA Carri MT Crosio C Iaccarino C LRRK2 affects vesicle trafficking. Neurotransmitter extracellular level and membrane receptor localizationPLoS One2013 8e77198

    Not in our library10.1371/journal.pone.0077198

  113. 113.

    MacLeod DA Rhinn H Kuwahara T Zolin A Di Paolo G McCabe BD Marder KS Honig LS Clark LN Small SA Abeliovich A RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson’s disease riskNeuron2013 77425439

    Not in our library10.1016/j.neuron.2012.11.033

  114. 114.

    Ravikumar B Imarisio S Sarkar S O’Kane CJ Rubinsztein DC Rab5 modulates aggregation and toxicity of mutant huntingtin through macroautophagy in cell and fly models of Huntington diseaseJ Cell Sci2008 12116491660

    Not in our library10.1242/jcs.025726

  115. 115.

    Stow JL Manderson AP Murray RZ SNAREing immunity: the role of SNAREs in the immune systemNat Rev Immunol2006 6919929

    Not in our library10.1038/nri1980

  116. 116.

    Stanley AC Lacy P Pathways for cytokine secretionPhysiology (Bethesda)2010 25218229

    Not in our library10.1152/physiol.00017.2010

  117. 117.

    Stow JL Low PC Offenhauser C Sangermani D Cytokine secretion in macrophages and other cells: pathways and mediatorsImmunobiology2009 214601612

    Not in our library10.1016/j.imbio.2008.11.005

  118. 118.

    Lucin KM Wyss-Coray T Immune activation in brain aging and neurodegeneration: too much or too little?Neuron2009 64110122

    Not in our library10.1016/j.neuron.2009.08.039

  119. 119.

    Bucci C Bakke O Progida C Rab7b and receptors traffickingCommun Integr Biol2010 3401404

    Not in our library10.4161/cib.3.5.12341

  120. 120.

    Stuart LM Ezekowitz RA Phagocytosis: elegant complexityImmunity2005 22539550

    Not in our library10.1016/j.immuni.2005.05.002

  121. 121.

    Imamura K Hishikawa N Sawada M Nagatsu T Yoshida M Hashizume Y Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson’s disease brainsActa Neuropathol2003 106518526

    Not in our library10.1007/s00401-003-0766-2

  122. 122.

    Ghosh A Roy A Liu X Kordower JH Mufson EJ Hartley DM Ghosh S Mosley RL Gendelman HE Pahan K Selective inhibition of NF-kappaB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson’s diseaseProc Natl Acad Sci USA2007 1041875418759

    Not in our library10.1073/pnas.0704908104

  123. 123.
    LRRK2 kinase activity is dependent on LRRK2 GTP binding capacity but independent of LRRK2 GTP binding. · 2011
    Not checked

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