{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:51:11Z","timestamp":1785297071107,"version":"3.55.0"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"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":[[2025,9,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>This study explores the potential inhibitory effects of Synta-66 at doses of 1 and 5\u00a0mg\/kg, with a particular emphasis on the role of ORAI-I in amyloidogenesis, a common mechanism that underlies type-2 diabetes mellitus (T2DM) and Alzheimer\u2019s disease (AD).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Induction of T2DM-induced AD by the high-fat diet (HFD)-Streptozotocin (STZ)-A\u03b225\u201335 model. Assessment of behavioral parameters like polydipsia, polyphagia, Morris water maze, and passive avoidance test; biochemical estimation of glucose, insulin, oxidative stress (superoxide dismutase (SOD), glutathione (GSH), catalase (Cat), and thiobarbituric acid reactive substances (TBARS)), neuroinflammation (interleukin-1 beta (IL-1\u03b2), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-\u03b1), and nuclear factor-kappa B (NF-\u03ba\u03b2)), A\u03b2 level, through ELISA technique, and calcium levels via atomic absorption spectrometer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>Synta-66 (5 and 10\u00a0mg\/kg) results in a reduction in food and water intake, as well as a reduction in memory impairment in the Morris water maze and passive avoidance test. Furthermore, it normalizes glucose, insulin, and antioxidant elements (SOD, GSH, and Cat) level, while decreasing TBARS levels. In addition, ELISA data demonstrated a reduction in neuroinflammation (downregulation of IL-1\u03b2, IL-6, TNF-\u03b1, and NF-\u03ba\u03b2), A\u03b2 accumulation, and calcium levels by Synta-66 (5 and 10\u00a0mg\/kg).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Consequently, ORAI can play a crucial role in the mediation of amyloidogenesis induced by T2DM, thereby establishing a connection between T2DM and AD. Therefore, Synta-66 has the potential to treat and prevent the progression of T2DM to AD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jpp\/rgaf036","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T08:03:30Z","timestamp":1747123410000},"page":"1222-1243","source":"Crossref","is-referenced-by-count":2,"title":["Investigating the neuroprotective role of Synta-66 in type-2 diabetes mellitus-induced dementia in rats"],"prefix":"10.1093","volume":"77","author":[{"given":"Ashi","family":"Mannan","sequence":"first","affiliation":[{"name":"Chitkara College of Pharmacy, Chitkara University , Rajpura\u00a0, Punjab 140401 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maneesh","family":"Mohan","sequence":"additional","affiliation":[{"name":"Chitkara College of Pharmacy, Chitkara University , Rajpura\u00a0, Punjab 140401 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