{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:58:22Z","timestamp":1792807102965,"version":"4.5.0"},"reference-count":172,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>4-Phenylbutyrate (4-PBA), initially recognized for treating urea cycle disorders, has emerged as a potent therapeutic agent with broad-spectrum potential. As a chemical chaperone, 4-PBA modulates protein folding and reduces endoplasmic reticulum stress. 4-PBA has demonstrated efficacy in treating ocular herpes simplex virus type 1 (HSV-1) infection and HSV-1-induced encephalitis, highlighting its potential as a novel anti-herpetic therapy. Beyond its antiviral properties, 4-PBA\u2019s therapeutic reach extends to neurological disorders linked to HSV-1 infection, including Parkinson\u2019s, Alzheimer\u2019s, Huntington\u2019s diseases, and primary open-angle glaucoma. Furthermore, 4-PBA shows promise in treating a diverse array of conditions beyond neurology. Its potential has been explored in atherosclerosis, Adriamycin-induced cardiac injury, non-alcoholic fatty liver disease, rifamycin-induced liver injury, chronic kidney disease, diabetic nephropathy, NSAID-induced kidney injury, and chronic wound healing. This review synthesizes the multifaceted therapeutic potential of 4-PBA, emphasizing its role as a broad-spectrum agent capable of addressing a wide range of pathological conditions, particularly its role in combating HSV-1 and associated neurological disorders. The growing evidence suggests that 4-PBA may be a versatile and valuable addition to the therapeutic arsenal against multiple diseases.<\/jats:p>","DOI":"10.3389\/fphar.2025.1621590","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T05:29:04Z","timestamp":1755754144000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Broad-spectrum therapeutic potential of 4-phenylbutyrate in neurological and systemic diseases of viral and non-viral origin"],"prefix":"10.3389","volume":"16","author":[{"given":"Fatima","family":"Bobat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Kapoor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph S.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chima","family":"Orameh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tejabhiram","family":"Yadavalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhijit","family":"Date","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Shukla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.13188\/2334-2838.1000017","article-title":"The trabecular meshwork: a basic review of form and function","volume":"2","author":"Abu-Hassan","year":"2014","journal-title":"J. ocular Biol."},{"key":"B2","doi-asserted-by":"crossref","DOI":"10.2337\/db20211-2","article-title":"Pathogenesis of diabetic nephropathy","volume-title":"Chronic kidney disease and type 2 diabetes","author":"Agarwal","year":"2021"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2360","DOI":"10.1182\/blood-2008-02-137711","article-title":"Requirement of TLR2-mediated signaling for the induction of IL-15 gene expression in human monocytic cells by HSV-1","volume":"112","author":"Ahmad","year":"2008","journal-title":"Blood"},{"key":"B4","doi-asserted-by":"publisher","first-page":"259","DOI":"10.31887\/DCNS.2004.6.3\/galexander","article-title":"Biology of Parkinson\u2019s disease: pathogenesis and pathophysiology of a multisystem neurodegenerative disorder","volume":"6","author":"Alexander","year":"2004","journal-title":"Dialogues Clin. 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