Muscle Cathepsin B benefits Alzheimer's Disease mice

ABSTRACT: Muscle secretes factors during exercise that enhance cognition. Myokine Cathepsin B (Ctsb) is linked to memory, but its role in neurodegeneration is unclear. Here we show that AAV-vector-mediated Ctsb overexpression in skeletal muscle, in an Alzheimer’s Disease (AD) mouse model (APP/PS1), improved motor coordination, memory and adult hippocampal neurogenesis, while plaque density was unchanged. Conversely, in wildtype (WT) mice Ctsb impaired memory. To understand underlying mechanisms, hippocampus, muscle and plasma proteomic analyses were performed. In AD mice, Ctsb treatment increased abundance of hippocampal proteins involved in mRNA metabolism and protein synthesis. In muscle, Ctsb treatment increased protein translation in AD mice, whereas in WT mitochondrial proteins decreased. Additionally, in AD mice Ctsb enhanced plasma metabolic and mitochondrial processes, and reduced inflammatory responses. The differing protein abundance profiles in the AD and WT treatment groups correspond to effects on memory function. Overall, skeletal muscle Ctsb expression is a potential AD therapeutic.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Skeletal Muscle, Blood Plasma

SUBMITTER: Hazal Haytural  

LAB HEAD: Atul Deshmukh

PROVIDER: PXD057069 | Pride | 2025-11-17

REPOSITORIES: Pride