Ca_V2.1 mediates presynaptic dysfunction induced by amyloid β oligomers.

ABSTRACT: Synaptic dysfunction is an early pathological phenotype of Alzheimer's disease (AD) that is initiated by oligomers of amyloid β peptide (Aβ_os). Treatments aimed at correcting synaptic dysfunction could be beneficial in preventing disease progression, but mechanisms underlying Aβ_o-induced synaptic defects remain incompletely understood. Here, we uncover an epithelial sodium channel (ENaC) - Ca_V2.3 - protein kinase C (PKC) - glycogen synthase kinase-3β (GSK-3β) signal transduction pathway that is engaged by Aβ_os to enhance presynaptic Ca_V2.1 voltage-gated Ca²⁺ channel activity, resulting in pathological potentiation of action-potential-evoked synaptic vesicle exocytosis. We present evidence that the pathway is active in human

SUBMITTER: Jeans AF 

PROVIDER: S-EPMC12799594 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature