The Role of CAPNS1 in Mitochondrial Function and Synaptic Plasticity of Alzheimer's Disease

ABSTRACT: Alzheimer's disease (AD), a neurodegenerative disorder, is marked by brain atrophy. Beyond the recognized and dominant amyloid cascade hypothesis, mitochondrial dysfunction contributes to AD progression. Improving mitochondrial function has been found to rescue cognitive deficits in AD. However, the relevant mechanisms are poorly understood. Our study revealed decreased levels of calpain small subunit 1 (CAPNS1) levels in AD, which was correlated with mitochondrial dysfunction and synaptic loss. This study demonstrated that CAPNS1 regulated mitochondrial DNA (mtDNA) expression by activating the Ca2+-CaMKⅡβ-MAPK-PGC-1α axis, thereby improving mitochondrial function. In addition, CAPNS1 upregulation in the APP/PS1 mice improved synaptic plasticity and cognitive function. Collectively, CAPNS1, as a pivotal regulator of mitochondrial function, alleviated synaptic loss and cognitive defect in AD.

ORGANISM(S): Mus musculus

PROVIDER: GSE329819 | GEO | 2026/08/31

REPOSITORIES: GEO