{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T07:16:40Z","timestamp":1783322200096,"version":"3.54.6"},"reference-count":142,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DE017102"],"award-info":[{"award-number":["R01DE017102"]}],"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":["R01DE031716"],"award-info":[{"award-number":["R01DE031716"]}],"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":["R01DE032317"],"award-info":[{"award-number":["R01DE032317"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Salivary gland hypofunction and xerostomia represent major clinical complications of radiation therapy, autoimmune disorders such as Sj\u00f6gren's disease, and inherited epithelial ion transport defects. This review integrates current knowledge on ion channel dysfunction as a central mechanistic driver of salivary gland pathology and evaluates promising ion channel\u2010targeted therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A comprehensive narrative review was performed using PubMed, Scopus, and Web of Science to identify experimental, translational, and clinical studies on ion channel regulation in salivary gland physiology and disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Salivary secretion depends on coordinated Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signaling and polarized ion transport in acinar and ductal cells. Across radiation injury, Sj\u00f6gren's disease, and cystic fibrosis, disease\u2010specific disruptions of calcium entry, chloride conductance, and water channel trafficking converge on impaired fluid secretion through distinct but mechanistically overlapping pathways. These insights have driven targeted therapies, including muscarinic agonists, ANO1 and CFTR modulators, anti\u2010inflammatory strategies, and AAV2\u2010hAQP1 gene therapy, which shows sustained benefit in radiation\u2010induced xerostomia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ion channels are central regulators of salivary gland physiology and promising therapeutic targets, and combining pharmacologic, gene, and regenerative approaches provides a precision strategy to restore salivary gland function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/odi.70419","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T06:59:59Z","timestamp":1783321199000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ion Channel Dysfunction and Therapeutic Targeting in Salivary Gland Disorders"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3441-9673","authenticated-orcid":false,"given":"Tarek Mohamed","family":"Abd El\u2010Aziz","sequence":"first","affiliation":[{"name":"Center for Regenerative Sciences, School of Dentistry University of Texas Health Science Center San Antonio  San Antonio Texas USA"},{"name":"Zoology Department, Faculty of Science Minia University  El\u2010Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shankara N.","family":"Varadarajan","sequence":"additional","affiliation":[{"name":"Center for Regenerative Sciences, School of Dentistry University of Texas Health Science Center San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Drel","sequence":"additional","affiliation":[{"name":"Center for Regenerative Sciences, School of Dentistry University of Texas Health Science Center San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash","family":"Arullampalam","sequence":"additional","affiliation":[{"name":"Center for Regenerative Sciences, School of Dentistry University of Texas Health Science Center San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud I.","family":"Shoulkamy","sequence":"additional","affiliation":[{"name":"Zoology Department, Faculty of Science Minia University  El\u2010Minia Egypt"},{"name":"Department of Biology, Faculty of Education and Arts Sohar University  Sohar Sultanate of Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Al\u2010Sabi","sequence":"additional","affiliation":[{"name":"College of Integrative Studies Abdullah Al Salem University  Khaldiya Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brij B.","family":"Singh","sequence":"additional","affiliation":[{"name":"Center for Regenerative Sciences, School of Dentistry University of Texas Health Science Center San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,5]]},"reference":[{"issue":"4","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","DOI":"10.3390\/cells15040369","article-title":"Ion Channel Integration and Functional Coupling in Salivary Gland Fluid Secretion","volume":"15","author":"Abd El\u2010Aziz T. 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