{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:21:22Z","timestamp":1788805282917,"version":"build-2803163510"},"reference-count":87,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e1 e della Ricerca","doi-asserted-by":"publisher","award":["2017WJZ9W9"],"award-info":[{"award-number":["2017WJZ9W9"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Clin. Diabetes Healthc."],"abstract":"<jats:p>WFS1 spectrum disorder (WFS1-SD) is a rare monogenic neurodegenerative disorder whose cardinal symptoms are childhood-onset diabetes mellitus, optic atrophy, deafness, diabetes insipidus, and neurological signs ranging from mild to severe. The prognosis is poor as most patients die prematurely with severe neurological disabilities such as bulbar dysfunction and organic brain syndrome. Mutation of the <jats:italic>WFS1<\/jats:italic> gene is recognized as the prime mover of the disease and responsible for a dysregulated ER stress signaling, which leads to neuron and pancreatic \u03b2-cell death. There is no currently cure and no treatment that definitively arrests the progression of the disease. GLP-1 receptor agonists appear to be an efficient way to reduce elevated ER stress <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, and increasing findings suggest they could be effective in delaying the progression of WFS1-SD. Here, we summarize the characteristics of GLP-1 receptor agonists and preclinical and clinical data obtained by testing them in WFS1-SD as a feasible strategy for managing this disease.<\/jats:p>","DOI":"10.3389\/fcdhc.2023.1171091","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T12:11:05Z","timestamp":1685707865000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["GLP-1 receptor agonists as promising disease-modifying agents in WFS1 spectrum disorder"],"prefix":"10.3389","volume":"4","author":[{"given":"Eleonora","family":"Panfili","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Frontino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Pallotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,2]]},"reference":[{"key":"B1","article-title":"WFS1 spectrum disorder","volume-title":"GeneReviews(\u00ae)","author":"Barrett","year":"1993"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.18.12.1566","article-title":"Morbidity and mortality in the wolfram syndrome","volume":"18","author":"Kinsley","year":"1995","journal-title":"Diabetes Care"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1086\/520961","article-title":"A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for wolfram syndrome 2","volume":"81","author":"Amr","year":"2007","journal-title":"Am J Hum Genet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1186\/s12967-019-1993-1","article-title":"Wolfram syndrome, a rare neurodegenerative disease: from pathogenesis to future treatment perspectives","volume":"17","author":"Pallotta","year":"2019","journal-title":"J Transl Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"3225","DOI":"10.3390\/ijerph19063225","article-title":"Wolfram syndrome 1: from genetics to therapy","volume":"19","author":"Rigoli","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/Jfebslet.2006.09.007","article-title":"WFS1 protein modulates the free Ca(2+) concentration in the endoplasmic reticulum","volume":"580","author":"Takei","year":"2006","journal-title":"FEBS Lett"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39678","article-title":"Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells","volume":"120","author":"Fonseca","year":"2010","journal-title":"J Clin Invest"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.ircmb.2021.03.003","article-title":"Calcium signaling and endoplasmic reticulum stress","volume":"363","author":"Groenendyk","year":"2021","journal-title":"Int Rev Cell Mol Biol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14608","article-title":"Endoplasmic reticulum stress signalling - from basic mechanisms to clinical applications","volume":"286","author":"Almanza","year":"2019","journal-title":"FEBS J"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaq1380","article-title":"ER-mitochondria cross-talk is regulated by the Ca(2+) sensor NCS1 and is impaired in wolfram syndrome","volume":"11","author":"Angebault","year":"2018","journal-title":"Sci. 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