Amyloid-β Induces Cdh1-Mediated Rock2 Stabilization Causing Neurodegeneration.

ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, which is causally related to the accumulation of abnormally folded amyloid-β (Aβ) peptide and hyperphosphorylated tau protein aggregates. The dendritic spine regulator Rho protein kinase 2 (Rock2) accumulates in the brain at the earliest stages of AD and remains increased during disease progression. However, the molecular mechanism that upregulates Rock2 in AD, and its role in the disease progression, are unknown. Here, we found that oligomers of the amyloidogenic fragment 25-35 of the Aβ peptide (Aβ25-35) trigger Rock2 accumulation and activation in mouse cortical neurons in primary culture and in mouse hippocampus in vivo. Neuronal apoptotic death and memory impairment caused b

SUBMITTER: Lapresa R 

PROVIDER: S-EPMC9047900 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature