{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:26:01Z","timestamp":1791861961301,"version":"4.3.4"},"reference-count":96,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T00:00:00Z","timestamp":1766793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic alcohol exposure induces complex pathophysiological changes in the central nervous system (CNS), contributing to the onset and progression of neurodegenerative disorders. This review integrates recent findings on ethanol-induced neurotoxicity, focusing on key mechanisms including oxidative stress, protein misfolding, mitochondrial dysfunction, calcium dysregulation, neuroinflammation, and epigenetic alterations. We further discuss the detrimental impact of ethanol metabolism particularly its neurotoxic intermediates such as acetaldehyde and salsolinol on neuronal integrity. Special emphasis is placed on glial cell activation, blood\u2013brain barrier disruption, and dysregulation of survival pathways such as PI3K\/Akt\/mTOR. Finally, we highlight promising therapeutic strategies targeting these molecular and cellular disruptions. A comprehensive understanding of these processes is critical for the development of neuroprotective interventions aimed at mitigating alcohol-related cognitive and functional decline.<\/jats:p>","DOI":"10.3390\/ijms27010299","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T05:28:19Z","timestamp":1766986099000},"page":"299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Neurotoxicity of Chronic Alcohol Exposure: Mechanistic Insights, Cellular Disruption, and Emerging Therapeutic Strategies"],"prefix":"10.3390","volume":"27","author":[{"given":"Philip","family":"Go\u0142aszewski","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, University of Rzesz\u00f3w, 35-516 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8568-1770","authenticated-orcid":false,"given":"Agata","family":"Wawrzyniak","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, University of Rzesz\u00f3w, 35-516 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1057-9656","authenticated-orcid":false,"given":"Maksymilian","family":"K\u0142osowicz","sequence":"additional","affiliation":[{"name":"Department of Normal and Clinical Anatomy, Faculty of Medicine, University of Rzesz\u00f3w, 35-516 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Burbelka","sequence":"additional","affiliation":[{"name":"Department of Normal and Clinical Anatomy, Faculty of Medicine, University of Rzesz\u00f3w, 35-516 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Balawender","sequence":"additional","affiliation":[{"name":"Department of Normal and Clinical Anatomy, Faculty of Medicine, University of Rzesz\u00f3w, 35-516 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.5582\/bst.2021.01041","article-title":"The role of Toll-like receptors in neurobiology of alcoholism","volume":"15","author":"Airapetov","year":"2021","journal-title":"Biosci. 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