Amyloid precursor protein and C99 are subunits in human microglial Hv1 channels that enhance current and inflammatory mediator release.

ABSTRACT: In Alzheimer's disease (AD), hyperactivated microglia produce inflammatory mediators that contribute to neuroinflammation and neuronal damage. Amyloid precursor protein (APP), a transmembrane protein expressed in many cell types, including neurons and microglia, plays a critical role in AD pathogenesis via its secretase-mediated processing to release the C-terminal 99-residue transmembrane fragment (C99) that is further cleaved to yield amyloid-β peptides. Voltage-gated proton channels (Hv1) have been implicated in microglial activation and release of inflammatory mediators, but the potential role of these channels in human microglia and AD pathogenesis remains unclear. Here, we demonstrate that human induced pluripotent stem cell-derived microglia (iMG) express native Hv1 channels with bi

SUBMITTER: Zhao R 

PROVIDER: S-EPMC12582281 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature