{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T18:43:56Z","timestamp":1774982636520,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T00:00:00Z","timestamp":1715990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2P30AG038070-06A2"],"award-info":[{"award-number":["2P30AG038070-06A2"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R35GM133588-01A1"],"award-info":[{"award-number":["1R35GM133588-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2P30AG038070-06A2"],"award-info":[{"award-number":["2P30AG038070-06A2"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R35GM133588-01A1"],"award-info":[{"award-number":["1R35GM133588-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Age is the primary risk factor for neurodegenerative diseases such as Alzheimer\u2019s and Huntington\u2019s disease. Alzheimer\u2019s disease is the most common form of dementia and a leading cause of death in the elderly population of the United States. No effective treatments for these diseases currently exist. Identifying effective treatments for Alzheimer\u2019s, Huntington\u2019s, and other neurodegenerative diseases is a major current focus of national scientific resources, and there is a critical need for novel therapeutic strategies. Here, we investigate the potential for targeting the kynurenine pathway metabolite 3-hydroxyanthranilic acid (3HAA) using Caenorhabditis elegans expressing amyloid-beta or a polyglutamine peptide in body wall muscle, modeling the proteotoxicity in Alzheimer\u2019s and Huntington\u2019s disease, respectively. We show that knocking down the enzyme that degrades 3HAA, 3HAA dioxygenase (HAAO), delays the age-associated paralysis in both models. This effect on paralysis was independent of the protein aggregation in the polyglutamine model. We also show that the mechanism of protection against proteotoxicity from HAAO knockdown is mimicked by 3HAA supplementation, supporting elevated 3HAA as the mediating event linking HAAO knockdown to delayed paralysis. This work demonstrates the potential for 3HAA as a targeted therapeutic in neurodegenerative disease, though the mechanism is yet to be explored.<\/jats:p>","DOI":"10.3390\/biom14050599","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T11:06:41Z","timestamp":1716203201000},"page":"599","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["3-Hydroxyanthranilic Acid Delays Paralysis in Caenorhabditis elegans Models of Amyloid-Beta and Polyglutamine Proteotoxicity"],"prefix":"10.3390","volume":"14","author":[{"given":"Bradford T.","family":"Hull","sequence":"first","affiliation":[{"name":"Molecular and Cellular Biology Department, University of Arizona, Tucson, AZ 85721, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7811-3975","authenticated-orcid":false,"given":"Kayla M.","family":"Miller","sequence":"additional","affiliation":[{"name":"Cancer Biology Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ 85721, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Corban","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grant","family":"Backer","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Sheehan","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ron","family":"Korstanje","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3659-4678","authenticated-orcid":false,"given":"George L.","family":"Sutphin","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology Department, University of Arizona, Tucson, AZ 85721, USA"},{"name":"Cancer Biology Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ 85721, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Xu, J., Murphy, S.L., Kochanek, K.D., and Arias, E. 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