{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:15:17Z","timestamp":1760058917506,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple Sclerosis (MS) is a chronic autoimmune disorder characterized by demyelination and neuronal damage in the central nervous system. Dysregulation of calcium homeostasis, particularly through the Store-Operated Calcium Entry-Associated Regulatory Factor (SARAF), has been implicated in MS pathogenesis. This study investigated SARAF, STIM1, and Orai1 expression patterns and their relationship to calcium homeostasis in 45 Bahraini MS patients and 45 matched healthy controls using ELISA and real-time PCR analyses. MS patients showed significantly elevated serum SARAF levels in both early (192.26 \u00b1 47.00 pg\/mL) and late MS stages (341.47 \u00b1 96.19 pg\/mL) compared to controls (129.82 \u00b1 30.82 pg\/mL; p &lt; 0.001. SARAF expressions were markedly increased in MS patients (3.829 \u00b1 0.04422 vs. 1 \u00b1 0; p &lt; 0.0001), while STIM1 (0.4324 \u00b1 0.01471) and ORAI1 (0.2963 \u00b1 0.02156) expressions were significantly reduced compared to the controls (p &lt; 0.0001). Intracellular calcium levels were notably elevated in both early and late MS stages. These findings suggest that the progressive elevation of SARAF, coupled with altered STIM1 and ORAI1 expression, may serve as potential biomarkers for MS progression and represent promising therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms26104520","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T04:13:44Z","timestamp":1746764024000},"page":"4520","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Progressive Elevation of Store-Operated Calcium Entry-Associated Regulatory Factor (SARAF) and Calcium Pathway Dysregulation in Multiple Sclerosis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8276-4535","authenticated-orcid":false,"given":"Safa","family":"Taha","sequence":"first","affiliation":[{"name":"Princess Al Jawhara Center for Molecular Medicine, Genetics and Inherited Diseases, Department of Molecular Medicine, College of Medicine and Health Sciences, Arabian Gulf University, Manama P.O. Box 26671, Bahrain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1178-8625","authenticated-orcid":false,"given":"Muna","family":"Aljishi","sequence":"additional","affiliation":[{"name":"Princess Al Jawhara Center for Molecular Medicine, Genetics and Inherited Diseases, Department of Molecular Medicine, College of Medicine and Health Sciences, Arabian Gulf University, Manama P.O. Box 26671, Bahrain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6660-3627","authenticated-orcid":false,"given":"Ameera","family":"Sultan","sequence":"additional","affiliation":[{"name":"Princess Al Jawhara Center for Molecular Medicine, Genetics and Inherited Diseases, Department of Molecular Medicine, College of Medicine and Health Sciences, Arabian Gulf University, Manama P.O. Box 26671, Bahrain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moudi E.","family":"Al-Nashmi","sequence":"additional","affiliation":[{"name":"Princess Al Jawhara Center for Molecular Medicine, Genetics and Inherited Diseases, Department of Molecular Medicine, College of Medicine and Health Sciences, Arabian Gulf University, Manama P.O. Box 26671, Bahrain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5148-8849","authenticated-orcid":false,"given":"Moiz","family":"Bakhiet","sequence":"additional","affiliation":[{"name":"Princess Al Jawhara Center for Molecular Medicine, Genetics and Inherited Diseases, Department of Molecular Medicine, College of Medicine and Health Sciences, Arabian Gulf University, Manama P.O. Box 26671, Bahrain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8101-7108","authenticated-orcid":false,"given":"Salvatore","family":"Spicuglia","sequence":"additional","affiliation":[{"name":"Aix-Marseille University, INSERM, TAGC, UMR1090, Equipe Lab\u00e9lis\u00e9e Ligue Contre le Cancer, 13288 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9523-0658","authenticated-orcid":false,"given":"Mohamed","family":"Belhocine","sequence":"additional","affiliation":[{"name":"Princess Al Jawhara Center for Molecular Medicine, Genetics and Inherited Diseases, Department of Molecular Medicine, College of Medicine and Health Sciences, Arabian Gulf University, Manama P.O. Box 26671, Bahrain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1172\/JCI21357","article-title":"Multiple sclerosis","volume":"113","author":"Hafler","year":"2004","journal-title":"J. Clin. 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