No retraction, correction or concern found when last checked on Oct 16, 2026.

A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Nanotherapeutics

Richard N. L. Lamptey, Bivek Chaulagain, Riddhi Trivedi and 3 more

International Journal of Molecular Sciences · 2022 · Review · CC BY

Abstract

Neurodegenerative disorders are primarily characterized by neuron loss. The most common neurodegenerative disorders include Alzheimer’s and Parkinson’s disease. Although there are several medicines currently approved for managing neurodegenerative disorders, a large majority of them only help with associated symptoms. This lack of pathogenesis-targeting therapies is primarily due to the restrictive effects of the blood–brain barrier (BBB), which keeps close to 99% of all “foreign substances” out of the brain. Since their discovery, nanoparticles have been successfully used for targeted delivery into many organs, including the brain. This review briefly describes the pathophysiology of Alzheimer’s, Parkinson’s disease, and amyotrophic lateral sclerosis, and their current management approaches. We then highlight the major challenges of brain-drug delivery, followed by the role of nanotherapeutics for the diagnosis and treatment of various neurological disorders.

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Huang C.L., Hsiao I.L., Lin H.C., Wang C.F., Huang Y.J., Chuang C.Y. Silver nanoparticles affect on gene expression of inflammatory and neurodegenerative responses in mouse brain neural cells. Environ. Res. 2015;136:253-263.
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Rajendran K., Anwar A., Khan N.A., Siddiqui R. Brain-eating amoebae: Silver nanoparticle conjugation enhanced efficacy of anti-amoebic drugs against Naegleria fowleri. ACS Chem. Neurosci. 2017;8:2626-2630.
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Gonzalez-Carter D.A., Leo B.F., Ruenraroengsak P., Chen S., Goode A.E., Theodorou I.G., Chung K.F., Carzaniga R., Shaffer M.S., Dexter D.T., et al. Silver nanoparticles reduce brain inflammation and related neurotoxicity through induction of H(2)S-synthesizing enzymes. Sci. Rep. 2017;7:42871.
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Skalska J., Strużyńska L. Toxic effects of silver nanoparticles in mammals—Does a risk of neurotoxicity exist? Folia Neuropathol. 2015;53:281-300.
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Bony B.A., Kievit F.M. A Role for Nanoparticles in Treating Traumatic Brain Injury. Pharmaceutics. 2019;11:473.
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Arya A., Gangwar A., Singh S.K., Roy M., Das M., Sethy N.K., Bhargava K. Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK-PKC-CBP signaling cascade. Int. J. Nanomed. 2016;11:1159.
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Pinzón-Daza M.L., Campia I., Kopecka J., Garzón R., Ghigo D., Riganti C. Nanoparticle- and liposome-carried drugs: New strategies for active targeting and drug delivery across blood-brain barrier. Curr. Drug Metab. 2013;14:625-640.
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Naz S., Beach J., Heckert B., Tummala T., Pashchenko O., Banerjee T., Santra S. Cerium oxide nanoparticles: A ‘radical’ approach to neurodegenerative disease treatment. Nanomedicine. 2017;12:545-553.
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Zavvari F., Nahavandi A., Shahbazi A. Neuroprotective effects of cerium oxide nanoparticles on experimental stress-induced depression in male rats. J. Chem. Neuroanat. 2020;106:101799.
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Wu M.-R., Lee C.-H., Hsiao J.-K. Bidirectional enhancement of cell proliferation between iron oxide nanoparticle-labeled mesenchymal stem cells and choroid plexus in a cell-based therapy model of ischemic stroke. Int. J. Nanomed. 2020;15:9181.
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Balducci C., Mancini S.A.-O., Minniti S., La Vitola P.A.-O., Zotti M., Sancini G., Mauri M., Cagnotto A., Colombo L.A.-O., Fiordaliso F., et al. Multifunctional liposomes reduce brain β-amyloid burden and ameliorate memory impairment in Alzheimer’s disease mouse models. J. Neurosci. 2014;34:14022-14031.
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Arora S., Layek B., Singh J. Design and validation of liposomal ApoE2 gene delivery system to evade blood–brain barrier for effective treatment of Alzheimer’s disease. Mol. Pharm. 2020;18:714-725.
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Arora S., Singh J. In vitro and in vivo optimization of liposomal nanoparticles based brain targeted vgf gene therapy. Int. J. Pharm. 2021;608:121095.
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Zhou H., S Beevers C., Huang S. The targets of curcumin. Curr. Drug Targets. 2011;12:332-347.
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Yanagisawa D., Amatsubo T., Morikawa S., Taguchi H., Urushitani M., Shirai N., Hirao K., Shiino A., Inubushi T., Tooyama I. In vivo detection of amyloid β deposition using ¹⁹F magnetic resonance imaging with a ¹⁹F-containing curcumin derivative in a mouse model of Alzheimer’s disease. Neuroscience. 2011;184:120-127.
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Lee I., Yang J., Lee J.H., Choe Y.S. Synthesis and evaluation of 1-(4-[¹⁸F]fluoroethyl)-7-(4’-methyl)curcumin with improved brain permeability for β-amyloid plaque imaging. Bioorganic Med. Chem. Lett. 2011;21:5765-5769.
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Bhatt R., Singh D., Prakash A., Mishra N. Development, characterization and nasal delivery of rosmarinic acid-loaded solid lipid nanoparticles for the effective management of Huntington’s disease. Drug Deliv. 2015;22:931-939.
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Sharma D., Singh J. Long-term glycemic control and prevention of diabetes complications in vivo using oleic acid-grafted-chitosan-zinc-insulin complexes incorporated in thermosensitive copolymer. J. Control. Release. 2020;323:161-178.
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128.
Baba M., Itaka K., Kondo K., Yamasoba T., Kataoka K. Treatment of neurological disorders by introducing mRNA in vivo using polyplex nanomicelles. J. Control. Release. 2015;201:41-48.
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Arora S., Trivedi R., Lamptey R.N., Chaulagain B., Layek B., Singh J. Smart biopolymers for controlled drug delivery applications. Tailor-Made and Functionalized Biopolymer Systems. 2021;53-83.
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Kim J.-Y., Choi W.I., Kim Y.H., Tae G. Brain-targeted delivery of protein using chitosan-and RVG peptide-conjugated, pluronic-based nano-carrier. Biomaterials. 2013;34:1170-1178.
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Layek B., Singh J. Amino acid grafted chitosan for high performance gene delivery: Comparison of amino acid hydrophobicity on vector and polyplex characteristics. Biomacromolecules. 2013;14:485-494.
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Xue Y., Wang N., Zeng Z., Huang J., Xiang Z., Guan Y.-Q. Neuroprotective effect of chitosan nanoparticle gene delivery system grafted with acteoside (ACT) in Parkinson’s disease models. J. Mater. Sci. Technol. 2020;43:197-207.
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Jaruszewski K.M., Ramakrishnan S., Poduslo J.F., Kandimalla K.K. Chitosan enhances the stability and targeting of immuno-nanovehicles to cerebro-vascular deposits of Alzheimer’s disease amyloid protein. Nanomed. Nanotechnol. Biol. Med. 2012;8:250-260.
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Cai Q., Wang L., Deng G., Liu J., Chen Q., Chen Z. Systemic delivery to central nervous system by engineered PLGA nanoparticles. Am. J. Transl. Res. 2016;8:749.
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Bhatt P.C., Verma A., Al-Abbasi F.A., Anwar F., Kumar V., Panda B.P. Development of surface-engineered PLGA nanoparticulate-delivery system of Tet1-conjugated nattokinase enzyme for inhibition of Aβ(40) plaques in Alzheimer’s disease. Int. J. Nanomed. 2017;12:8749.
Not in our library10.2147/ijn.s144545
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Carradori D., Balducci C., Re F., Brambilla D., Le Droumaguet B., Flores O., Gaudin A., Mura S., Forloni G., Ordoñez-Gutierrez L., et al. Antibody-functionalized polymer nanoparticle leading to memory recovery in Alzheimer’s disease-like transgenic mouse model. Nanotechnol. Biol. Med. 2018;14:609-618.
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Saffari P.M., Alijanpour S., Takzaree N., Sahebgharani M., Etemad-Moghadam S., Noorbakhsh F., Partoazar A. Metformin loaded phosphatidylserine nanoliposomes improve memory deficit and reduce neuroinflammation in streptozotocin-induced Alzheimer’s disease model. Life Sci. 2020;255:117861.
Not in our library10.1016/j.lfs.2020.117861
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Amini S., Saudi A., Amirpour N., Jahromi M., Najafabadi S.S., Kazemi M., Rafienia M., Salehi H. Application of electrospun polycaprolactone fibers embedding lignin nanoparticle for peripheral nerve regeneration: In vitro and in vivo study. Int. J. Biol. Macromol. 2020;159:154-173.
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Mili B., Das K., Kumar A., Saxena A., Singh P., Ghosh S., Bag S. Preparation of NGF encapsulated chitosan nanoparticles and its evaluation on neuronal differentiation potentiality of canine mesenchymal stem cells. J. Mater. Sci. Mater. Med. 2018;29:1-13.
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Zielińska A., Costa B., Ferreira M.V., Miguéis D., Louros J., Durazzo A., Lucarini M., Eder P., V Chaud M., Morsink M. Nanotoxicology and nanosafety: Safety-by-design and testing at a glance. Int. J. Environ. Res. Public Health. 2020;17:4657.
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Hofmann-Amtenbrink M., Hofmann H., Hool A., Roubert F. Nanotechnology in medicine: European research and its implications. Swiss Med. Wkly. 2014;144:w14044.
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Suk J.S., Xu Q., Kim N., Hanes J., Ensign L.M. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv. Drug Deliv. Rev. 2016;99:28-51.
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Neves A., van der Putten L., Queiroz J., Pinheiro M., Reis S. Transferrin-functionalized lipid nanoparticles for curcumin brain delivery. J. Biotechnol. 2021;331:108-117.
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Ji X., Lu W., Wu K., Cho W.C. Influencing Factors of the Pharmacokinetic Characters on Nanopharmaceutics. Pharm. Nanotechnol. 2017;5:24-31.
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Souto E.B., Silva G.F., Dias-Ferreira J., Zielinska A., Ventura F., Durazzo A., Lucarini M., Novellino E., Santini A. Nanopharmaceutics: Part II—Production scales and clinically compliant production methods. Nanomaterials. 2020;10:455.
Not in our library10.3390/nano10030455
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