{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:33:10Z","timestamp":1760146390747,"version":"build-2065373602"},"reference-count":77,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T00:00:00Z","timestamp":1730332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The WFS1 gene was first identified in Wolfram Syndrome 1 (WS1), a rare autosomal recessive genetic disorder characterized by severe and progressive neurodegenerative changes. WFS1\u2019s role in various cellular mechanisms, particularly in calcium homeostasis and the modulation of endoplasmic reticulum (ER) stress, suggests its potential involvement in the pathogenesis of Alzheimer\u2019s disease (AD) and sleep disorders. Because it is involved in maintaining ER balance, calcium signaling, and stress responses, WFS1 plays a multifaceted role in neuronal health. Numerous studies have shown that the absence or improper expression of WFS1 disrupts these cellular processes, leading to neurodegeneration and making neurons more vulnerable. In AD, WFS1 dysfunction is thought to contribute to the accumulation of amyloid-\u03b2 (A\u03b2) plaques and tau tangles, thereby accelerating disease progression. Additionally, WFS1 plays an essential role in sleep regulation by influencing neuronal excitability and neurotransmitter release, which may explain the sleep disturbances frequently observed in neurodegenerative diseases. Due to its involvement in the pathological mechanisms of AD and sleep disorders, WFS1 is regarded as a potential early diagnostic marker for these diseases. Further research is required to fully elucidate WFS1\u2019s role in the cellular pathway, perhaps facilitating the development of new therapeutic strategies for Alzheimer\u2019s disease and sleep disorders.<\/jats:p>","DOI":"10.3390\/biom14111389","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T06:55:37Z","timestamp":1730357737000},"page":"1389","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Beyond Wolfram Syndrome 1: The WFS1 Gene\u2019s Role in Alzheimer\u2019s Disease and Sleep Disorders"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1955-8074","authenticated-orcid":false,"given":"Valerio","family":"Caruso","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Psychiatric Section, Azienda Ospedaliera Universitaria Pisana (A.U.O.P.), 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1774-8173","authenticated-orcid":false,"given":"Luciana","family":"Rigoli","sequence":"additional","affiliation":[{"name":"Department of Human Pathology of Adulthood and Childhood G. Barresi, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/2441","article-title":"A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome)","volume":"20","author":"Inoue","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1093\/hmg\/7.13.2021","article-title":"Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein","volume":"7","author":"Strom","year":"1998","journal-title":"Hum. Mol. 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