{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T14:47:09Z","timestamp":1776178029127,"version":"3.50.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Huntington\u2019s disease (HD) is a neurodegenerative condition characterized by a gradual decline in motor skills, cognitive function, and mental health. The 3-nitropropionic acid (3-NPA) model simulates HD-like pathology, which involves calcium dysregulation. To establish a structural basis for targeting Orai-1, in-silico docking was conducted prior to assessing the neuroprotective effects of the Orai-1 inhibitor Synta-66 in a 3-NPA-induced HD model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mice were randomly divided into five groups (n\u2009=\u20098): normal control, 3-NPA (10\u00a0mg\/kg, i.p.), 3-NPA combined with tetrabenazine (3\u00a0mg\/kg, i.p.), 3-NPA combined with Synta-66 (5\u00a0mg\/kg, i.p.), and 3-NPA combined with Synta-66 (10\u00a0mg\/kg, i.p.). In-silico docking was used to evaluate the interactions of Synta-66 with Orai-1 and other targets related to neurodegeneration. Various parameters including behavioural, biochemical, oxidative stress, and neuroinflammatory markers were assessed. Additionally, the ELISA expression of Orai-1 protein and Ca2+ levels were measured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>In-silico analysis revealed that Synta-66 binds effectively with Orai-1 and its related targets. In vivo studies showed that 3-NPA caused notable motor impairments, biochemical changes, neuroinflammation, and disruptions in Ca2+ regulation. Administration of Synta-66 led to a dose-dependent recovery of body weight, enhancement of behavioural performance, normalization of biochemical and neuroinflammatory indicators, and a decrease in Orai-1 protein levels and intracellular Ca2+ concentrations, similar to the effects of tetrabenazine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The findings suggest the therapeutic potential of targeting Orai-1 channel using the inhibitor Synta-66 could serve as a neuroprotective treatment in a 3-NPA-induced HD model in mice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgag030","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T12:25:11Z","timestamp":1773663911000},"source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological evaluation of Orai-1 inhibitor in 3-nitropropionic acid-induced Huntington disease"],"prefix":"10.1093","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6061-2012","authenticated-orcid":false,"given":"Veerta","family":"Sharma","sequence":"first","affiliation":[{"name":"Chitkara College of Pharmacy, Chitkara University , Rajpura, Punjab 140401 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4242-3584","authenticated-orcid":false,"given":"Shareen","family":"Singh","sequence":"additional","affiliation":[{"name":"Chitkara College of Pharmacy, Chitkara University , Rajpura, Punjab 140401 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2979-1590","authenticated-orcid":false,"given":"Thakur Gurjeet","family":"Singh","sequence":"additional","affiliation":[{"name":"Chitkara College of Pharmacy, Chitkara University , Rajpura, Punjab 140401 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