{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T07:56:16Z","timestamp":1775202976911,"version":"3.50.1"},"reference-count":143,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"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>Alcohol use disorder (AUD) is highly comorbid with psychiatric conditions and is increasingly recognized as a modifiable factor associated with cognitive decline and dementia, including Alzheimer\u2019s disease (AD). While epidemiological and experimental studies consistently demonstrate that chronic alcohol exposure exacerbates neurodegenerative vulnerability rather than implying a single dominant causal pathway, accumulating evidence supports a multifactorial and context-dependent framework in which alcohol acts as a disease-modifying stressor that perturbs endogenous adaptive and resilience mechanisms. Hydrogen sulfide (H2S), involved in redox regulation, mitochondrial function, neuroinflammatory control, and vascular homeostasis, has emerged as a candidate pathway that may be indirectly affected by alcohol exposure and relevant to neurodegenerative processes. This narrative mechanistic review synthesizes preclinical and clinical data examining alcohol-induced perturbations and H2S-related signaling pathways in the context of AD. We analyzed studies on the effects of acute and chronic alcohol exposure, as well as on cellular processes influenced by H2S bioavailability and signaling. Across experimental models and human studies, alcohol exposure was consistently associated with oxidative and mitochondrial stress, neuroinflammation, and vascular dysfunction\u2014processes that overlap with biological domains normally regulated by H2S. Alcohol-related cognitive impairment frequently occurs in the absence of proportional increases in classical AD pathology, suggesting that alcohol may accelerate disease progression through non-canonical mechanisms. H2S signaling confers resilience against oxidative, inflammatory, and mitochondrial stress, whereas reduced H2S bioavailability or disrupted sulfide-dependent signaling increases neuronal vulnerability and cognitive impairment. However, the available data do not support a unidirectional or exclusive role for H2S as an integrative driver of alcohol-related AD pathology. H2S signaling represents a biologically plausible convergent and modulatory pathway linking alcohol exposure to AD risk.<\/jats:p>","DOI":"10.3390\/ijms27031595","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T10:05:47Z","timestamp":1770372347000},"page":"1595","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Alcohol-Induced Dysregulation of Hydrogen Sulfide Signaling in Alzheimer\u2019s Disease\u2014Narrative Mechanistic Synthesis Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1084-7710","authenticated-orcid":false,"given":"Constantin","family":"Munteanu","sequence":"first","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Ia\u0219i, 700115 Ia\u0219i, Romania"},{"name":"University of Medicine and Pharmacy \u201cCarol Davila\u201d, 020022 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5703-985X","authenticated-orcid":false,"given":"Cristina","family":"Popescu","sequence":"additional","affiliation":[{"name":"University of Medicine and Pharmacy \u201cCarol Davila\u201d, 020022 Bucharest, Romania"},{"name":"Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital \u201cBagdasar-Arseni\u201d, 041915 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1369-3873","authenticated-orcid":false,"given":"Andreea-Iulia","family":"Vl\u0103dulescu-Trandafir","sequence":"additional","affiliation":[{"name":"University of Medicine and Pharmacy \u201cCarol Davila\u201d, 020022 Bucharest, Romania"},{"name":"Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital \u201cBagdasar-Arseni\u201d, 041915 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3818-6624","authenticated-orcid":false,"given":"Francisco","family":"Maraver","sequence":"additional","affiliation":[{"name":"Medical Hydrology Group, Department of Radiology and Rehabilitation, Complutense University of Madrid, 28040 Madrid, Spain"},{"name":"Professional School of Medical Hydrology, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Manuel","family":"Carbajo","sequence":"additional","affiliation":[{"name":"Medical Hydrology Group, Department of Radiology and Rehabilitation, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6346-8941","authenticated-orcid":false,"given":"Gelu","family":"Onose","sequence":"additional","affiliation":[{"name":"University of Medicine and Pharmacy \u201cCarol Davila\u201d, 020022 Bucharest, Romania"},{"name":"Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital \u201cBagdasar-Arseni\u201d, 041915 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0741-8329(92)90059-J","article-title":"Alzheimer\u2019s Disease and Alcoholism: Possible Interactions","volume":"9","author":"Freund","year":"1992","journal-title":"Alcohol"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kilian, C., Klinger, S., Rehm, J., and Manthey, J. 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