{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:47:33Z","timestamp":1793314053551,"version":"4.5.0"},"reference-count":129,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019345","name":"King Salman Center for Disability Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019345","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Glycogen Synthase Kinase-3 Beta (GSK3\u03b2), a multifunctional serine\/threonine kinase, plays a central role in cellular signaling pathways and autophagy regulation, processes critical to neurodegenerative diseases such as Alzheimer\u2019s disease, Parkinson\u2019s disease, Huntington\u2019s disease and Amyotrophic Lateral Sclerosis (ALS). Dysregulation of autophagy leads to the toxic accumulation of misfolded proteins and damaged organelles, contributing to neuronal loss in these disorders. This review explores the mechanistic interplay between GSK3\u03b2 and autophagy, highlighting its modulation through key pathways, including mTOR, AMPK and Bcl-2 and its direct impact on autophagy-related proteins such as Beclin-1 and LC3. This review systematically discusses the disease-specific roles of GSK3\u03b2 in autophagy dysregulation and protein aggregation, providing evidence from recent studies on neurodegenerative models. Additionally, therapeutic approaches targeting GSK3\u03b2 are evaluated, including preclinical and clinical trials of GSK3\u03b2 inhibitors and combination therapies with autophagy modulators, emphasizing their potential for improving neuroprotection and cellular homeostasis. Despite its promise, challenges such as off-target effects and pathway complexity remain significant. This review highlights the importance of GSK3\u03b2 as both a therapeutic target and a biomarker, offering avenues for future research into selective GSK3\u03b2 modulators that enhance autophagy and mitigate ND progression.<\/jats:p>","DOI":"10.3389\/fphar.2025.1693805","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T05:23:59Z","timestamp":1760937839000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["The dual role of glycogen synthase kinase-3 beta (GSK3\u03b2) in neurodegenerative pathologies: interplay between autophagy and disease progression"],"prefix":"10.3389","volume":"16","author":[{"given":"Hassan H.","family":"Alhassan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Komal","family":"Janiyani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malvi","family":"Surti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd","family":"Adnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitesh","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/s41572-021-00280-3","article-title":"Parkinson disease-associated cognitive impairment","volume":"7","author":"Aarsland","year":"2021","journal-title":"Nat. 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