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In this study, amyloid\u2010<jats:italic>\u03b2<\/jats:italic> (A<jats:italic>\u03b2<\/jats:italic>)\u2010induced <jats:italic>C. elegans<\/jats:italic> models of AD were used to elucidate the mechanisms underlying calcium homeostasis in AD. Calcium acetate increased the intracellular calcium content, exacerbated A<jats:italic>\u03b2<\/jats:italic><jats:sub>1\u201342<\/jats:sub> aggregation, which is closely associated with oxidative stress, aggravated neuronal degeneration and dysfunction, and shortened the lifespan of the <jats:italic>C<\/jats:italic>. <jats:italic>elegans<\/jats:italic> models. Ethylene glycol tetraacetic acid (EGTA) and nimodipine were used to decrease the intracellular calcium content. Both EGTA and nimodipine showed remarkable inhibitory effects on A<jats:italic>\u03b2<\/jats:italic><jats:sub>1\u201342<\/jats:sub> aggregations by increasing oxidative stress resistance. Moreover, both compounds significantly delayed the onset of A<jats:italic>\u03b2<\/jats:italic>\u2010induced paralysis, rescued memory deficits, ameliorated behavioral dysfunction, decreased the vulnerability of two major (GABAergic and dopaminergic) neurons and synapses, and extended the lifespan of the <jats:italic>C. elegans<\/jats:italic> AD models. Furthermore, RNA sequencing of nimodipine\u2010treated worms revealed numerous downstream differentially expressed genes related to calcium signaling. Nimodipine\u2010induced inhibition of selective voltage\u2010gated calcium channels was shown to activate other calcium channels of the plasma membrane (<jats:italic>clhm-1<\/jats:italic>) and endoplasmic reticulum (<jats:italic>unc-68<\/jats:italic>), in addition to sodium\u2010calcium exchanger channels (<jats:italic>ncx-1<\/jats:italic>). These channels collaborated to activate downstream events to resist oxidative stress through glutathione S\u2010transferase activity mediated by HPGD and <jats:italic>skn-1<\/jats:italic>, as verified by RNA interference. These results may be applied for the treatment of Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.1155\/2022\/8287633","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T23:35:05Z","timestamp":1669851305000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Suppression of Selective Voltage\u2010Gated Calcium Channels Alleviates Neuronal Degeneration and Dysfunction through Glutathione S\u2010Transferase\u2010Mediated Oxidative Stress Resistance in a <i>Caenorhabditis elegans<\/i> Model of Alzheimer\u2019s 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