KIBRA repairs synaptic plasticity and promotes resilience to tauopathy-related memory loss.

ABSTRACT: Synaptic plasticity is obstructed by pathogenic tau in the brain, representing a key mechanism that underlies memory loss in Alzheimer's disease (AD) and related tauopathies. Here, we define a mechanism for plasticity repair in vulnerable neurons using the C-terminus of the KIdney/BRAin (KIBRA) protein (CT-KIBRA). We show that CT-KIBRA restores plasticity and memory in transgenic mice expressing pathogenic human tau; however, CT-KIBRA did not alter tau levels or prevent tau-induced synapse loss. Instead, we find that CT-KIBRA binds to and stabilizes protein kinase Mζ (PKMζ) to maintain synaptic plasticity and memory despite tau-mediated pathogenesis. In humans we find that reduced KIBRA in brain and increased KIBRA in cerebrospinal fluid are associated with cognitive impairment and patholo

SUBMITTER: Kauwe G 

PROVIDER: S-EPMC10312627 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature