Soluble β-Amyloid Oligomers Selectively Upregulate TRPC3 in Excitatory Neurons via Calcineurin-Coupled NFAT.

ABSTRACT: To investigate how dysregulated transient receptor potential canonical channels (TRPCs) are associated with Alzheimer's disease (AD), we challenged primary neurons with amyloid-β (Aβ). Both the naturally secreted or synthetic Aβ oligomers (AβOs) induced long-lasting increased TRPC3 and downregulated the TRPC6 expression in mature excitatory neurons (CaMKIIα-high) via a Ca²⁺-dependent calcineurin-coupled NFAT transcriptionally and calpain-mediated protein degradation, respectively. The TRPC3 expression was also found to be upregulated in pyramidal neurons of human AD brains. The selective downregulation of the Trpc6 gene induced synaptotoxicity, while no significant effect was observed from the Trpc3-targeting siRNA, suggesting potentially differential roles of TRPC3 and 6

SUBMITTER: Wang Z 

PROVIDER: S-EPMC12155350 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature