{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:36:19Z","timestamp":1790638579924,"version":"4.1.0"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) are characterized by progressive loss of neurons and still lack curative treatment options. In this review, we describe current and developing therapeutic strategies that include viral vector-based gene delivery, antisense oligonucleotide (ASO) and RNA interference methods, stem cell transplantation, and genome editing technologies. Adeno-associated viruses (AAVs) and lentiviruses have been used for gene delivery in preclinical and clinical studies, while ASOs are under development to reduce expression of pathogenic proteins such as tau, \u03b1-synuclein, and mutant huntingtin. Cellular therapies, including mesenchymal stem cell (MSC)-based paracrine support and transplantation of neurons derived from induced pluripotent stem cells (iPSCs), are being evaluated, particularly in PD and AD. We also discuss important gene targets such as APOE4, GBA1, SCNA, and MAPT, and how treatment strategies may differ between monogenic and polygenic forms of these disorders. Lastly, we highlight recent efforts focused on genes like TREM2, PINK1, and progranulin, and examine their role in the future development of gene- and cell-based interventions.<\/jats:p>","DOI":"10.3389\/fmed.2025.1718669","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T06:40:59Z","timestamp":1767940859000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Viral and non-viral cellular therapies for neurodegeneration"],"prefix":"10.3389","volume":"12","author":[{"given":"Jyotsna","family":"Srivastav","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachin","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.neurobiolaging.2020.06.001","article-title":"Impact of APOE-\u03b54 carriage on the onset and rates of neocortical A\u03b2-amyloid deposition","volume":"95","author":"Burnham","year":"2020","journal-title":"Neurobiol Aging."},{"key":"B2","doi-asserted-by":"publisher","first-page":"S183","DOI":"10.3233\/JPD-212739","article-title":"Gene therapy for Parkinson's disease associated with GBA1 mutations","volume":"11","author":"Abeliovich","year":"2021","journal-title":"J Parkinsons Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.jalz.2012.11.007","article-title":"The global prevalence of dementia: a systematic review and metaanalysis","volume":"9","author":"Prince","year":"2013","journal-title":"Alzheimers Dement"},{"key":"B4","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/S2215-0366(19)30475-4","article-title":"The burden of mental disorders across the states of India: the Global Burden of Disease Study 1990\u20132017","volume":"7","author":"Sagar","year":"2020","journal-title":"Lancet Psychiatry."},{"key":"B5","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1089\/hum.2020.138","article-title":"Adeno-associated virus-based gene therapy for lifelong correction of genetic disease","volume":"31","author":"Brommel","year":"2020","journal-title":"Hum Gene Ther."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e00427","DOI":"10.1016\/j.neurot.2024.e00427","article-title":"Stem cell therapeutics and gene therapy for neurologic disorders","volume":"21","author":"Chen","year":"2024","journal-title":"Neurotherapeutics."},{"key":"B7","doi-asserted-by":"publisher","first-page":"785","DOI":"10.3390\/cells12050785","article-title":"Various AAV serotypes and their applications in gene therapy: an overview","volume":"12","author":"Issa","year":"2023","journal-title":"Cells."},{"key":"B8","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1126\/science.1171242","article-title":"Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy","volume":"326","author":"Cartier","year":"2009","journal-title":"Science"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1016\/S0140-6736(13)61939-X","article-title":"Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1\/2 trial","volume":"383","author":"Palfi","year":"2014","journal-title":"Lancet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"109777","DOI":"10.1016\/j.isci.2024.109777","article-title":"New AAV9 engineered variants with enhanced neurotropism and reduced liver off-targeting in mice and marmosets","volume":"27","author":"Giannelli","year":"2024","journal-title":"iScience."},{"key":"B11","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.omtm.2018.03.004","article-title":"A rationally engineered capsid variant of AAV9 for systemic CNS-directed and peripheral tissue-detargeted gene delivery in neonates","volume":"9","author":"Wang","year":"2018","journal-title":"Mol Ther Methods Clin Dev."},{"key":"B12","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s40035-025-00466-9","article-title":"Application of antisense oligonucleotide drugs in amyotrophic lateral sclerosis and Huntington's disease","volume":"14","author":"Ou","year":"2025","journal-title":"Transl Neurodegener."},{"key":"B13","doi-asserted-by":"publisher","first-page":"177529","DOI":"10.1016\/j.ejphar.2025.177529","article-title":"Oligonucleotide-based therapeutics for neurodegenerative disorders: focus on antisense oligonucleotides","volume":"998","author":"Mansour","year":"2025","journal-title":"Eur J Pharmacol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"6367","DOI":"10.1097\/JS9.0000000000001609","article-title":"Priyanka, Romashchenko V, Al-Hussain SA, Zaki MEA. 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