Temporary alteration of neuronal network communication is a protective response to redox imbalance that requires GPI-anchored prion protein.

ABSTRACT: Cellular prion protein (PrP^C) protects neurons against oxidative stress damage. This role is lost upon its misfolding into insoluble prions in prion diseases, and correlated with cytoskeletal breakdown and neurophysiological deficits. Here we used mouse neuronal models to assess how PrP^C protects the neuronal cytoskeleton, and its role in network communication, from oxidative stress damage. Oxidative stress was induced extrinsically by potassium superoxide (KO₂) or intrinsically by Mito-Paraquat (MtPQ), targeting the mitochondria. In mouse neural lineage cells, KO₂ was damaging to the cytoskeleton, with cells lacking PrP^C (PrP^-/-) damaged more than wild-type (WT) cells. In hippocampal slices, KO₂ acutely inhibited

SUBMITTER: Foliaki ST 

PROVIDER: S-EPMC10196843 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature