{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:16:28Z","timestamp":1791656188235,"version":"4.3.4"},"reference-count":130,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Neurodegenerative diseases, including Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), and amyotrophic lateral sclerosis (ALS; Lou Gehrig\u2019s disease), represent a growing global health burden characterized by progressive neuronal loss and functional decline. Despite decades of intensive research, effective disease-modifying therapies remain limited, underscoring the urgent need for innovative therapeutic strategies. This review highlights recent advances in the understanding of disease etiology and emerging treatment approaches, with a particular focus on modalities with translational potential. We discussed novel disease-modifying interventions, including gene and cell therapies, RNA-targeting strategies, and immunotherapies aimed at clearing misfolded proteins such as amyloid-\u03b2, tau, and \u03b1-synuclein. In parallel, we examined the evolving recognition of neuroinflammation and mitochondrial dysfunction as actionable therapeutic targets, alongside progress in precision medicine and biomarker-guided approaches that enable early diagnosis and individualized treatment. Additionally, we summarized developments in repurposed pharmacological agents, neuroprotective compounds, and lifestyle interventions, emphasizing the importance of integrative, multimodal strategies. Across AD, PD, and ALS, convergent molecular mechanisms, including protein misfolding, oxidative stress, and disrupted proteostasis, present opportunities for cross-disease therapeutic targeting. Finally, we addressed key challenges and future directions, including translating preclinical efficacy into clinical success, optimizing CNS-targeted delivery systems, and navigating ethical considerations surrounding gene editing and stem cell therapies.<\/jats:p>","DOI":"10.3390\/cells15100928","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T08:06:26Z","timestamp":1779696386000},"page":"928","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Emerging Therapeutic Strategies for Neurodegenerative Diseases: A Comprehensive Review of Recent Advances and Future Directions"],"prefix":"10.3390","volume":"15","author":[{"given":"Masood","family":"Sepehrimanesh","sequence":"first","affiliation":[{"name":"School of Biological Sciences, College of Applied and Natural Sciences, Louisiana Tech University, Ruston, LA 71272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Victoria","family":"Melen","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, College of Applied and Natural Sciences, Louisiana Tech University, Ruston, LA 71272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Yeasmin","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, College of Applied and Natural Sciences, Louisiana Tech University, Ruston, LA 71272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9427-5328","authenticated-orcid":false,"given":"Victor Adeleke","family":"Ojo","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, College of Applied and Natural Sciences, Louisiana Tech University, Ruston, LA 71272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisca","family":"Walden","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, College of Applied and Natural Sciences, Louisiana Tech University, Ruston, LA 71272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humaira","family":"Urmee","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, College of Applied and Natural Sciences, Louisiana Tech University, Ruston, LA 71272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"Etheridge","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, College of Applied and Natural Sciences, Louisiana Tech University, Ruston, LA 71272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aruna Kumari","family":"Nasu","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, College of Applied and Natural Sciences, Louisiana Tech University, Ruston, LA 71272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ding, B., and Sepehrimanesh, M. 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