{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:00:34Z","timestamp":1787029234539,"version":"build-2736575974"},"reference-count":176,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["1R25DA056016"],"award-info":[{"award-number":["1R25DA056016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Despite the growing morbidity associated with alcohol use disorder (AUD), current FDA-approved therapeutics fail to adequately address the condition. This is in part due to the complex systemic effects of ethanol (EtOH), which have particularly negative consequences on the gut\u2013liver\u2013brain axis. Importantly, two systemic mechanisms underlying the progression of AUD remain underemphasized in therapeutic development: thiamine deficiency and neuroinflammation. Alcohol-induced thiamine deficiency leads to reduced activity of key metabolic enzymes, thereby resulting in energy deficits, oxidative stress, and severe clinical implications. EtOH also activates TLR4 and NLRP3, both of which play critical roles in the regulation of neuroimmune responses. While research directly investigating the relationship between thiamine deficiency and neuroinflammation is still in its early stages, our review highlights the emerging connections between these two seemingly distinct pathomechanisms. Additionally, potential therapeutic approaches and targets for addressing AUD at a systemic level are discussed.<\/jats:p>","DOI":"10.3390\/pathophysiology32030034","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T03:47:26Z","timestamp":1751600846000},"page":"34","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Thiamine Deficiency and Neuroinflammation Are Important Contributors to Alcohol Use Disorder"],"prefix":"10.3390","volume":"32","author":[{"given":"Nikhila","family":"Kalapatapu","sequence":"first","affiliation":[{"name":"Institute for Addiction Science, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0803-5489","authenticated-orcid":false,"given":"Samantha G.","family":"Skinner","sequence":"additional","affiliation":[{"name":"Titus Family Department of Clinical Pharmacy, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma G.","family":"D\u2019Addezio","sequence":"additional","affiliation":[{"name":"Titus Family Department of Clinical Pharmacy, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srija","family":"Ponna","sequence":"additional","affiliation":[{"name":"Titus Family Department of Clinical Pharmacy, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Cadenas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daryl L.","family":"Davies","sequence":"additional","affiliation":[{"name":"Institute for Addiction Science, University of Southern California, Los Angeles, CA 90033, USA"},{"name":"Titus Family Department of Clinical Pharmacy, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Publishing. 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