Aerobic exercise facilitates p300 nuclear translocation via ADRB2-AMPKα signaling, leading to enhanced histone acetylation and mitigation of cognitive decline in APP/PS1 mice - PubMed
3 months ago
- #Alzheimer's disease
- #Epigenetics
- #Exercise neuroscience
- Aerobic exercise (AE) enhances cognitive resilience and reduces Alzheimer's disease (AD) risk via epigenetic mechanisms.
- Study combines epidemiological analysis (NHANES cohort) and Mendelian randomization to show PA's dose-dependent cognitive benefits and causal AD risk reduction.
- Transcriptomic analysis (GSE110298) identifies synaptic signaling and neurogenesis as key pathways influenced by exercise in AD patients.
- APP/PS1 mice undergoing 8-week AE showed reduced Aβ pathology, improved synaptic plasticity, and normalized synaptic protein expression.
- Mechanistically, AE activates ADRB2 → AMPKα phosphorylation → p300 nuclear translocation → increased histone H4K5/H4K12 acetylation → synaptic gene (e.g., GluN1) transcription.
- AMPKα inhibition (dorsomorphin) blocks AE-induced p300 nuclear translocation and synaptic improvements in mice.
- Findings reveal the ADRB2-AMPKα-p300 axis as a novel epigenetic pathway for exercise-mediated neuroprotection in AD.