Epigenetic control of microglial mitochondrial immunity by KAT7 drives Alzheimer's disease pathogenesis - PubMed
4 hours ago
- #Alzheimer's disease
- #epigenetics
- #neuroinflammation
- KAT7 histone acetyltransferase is elevated in microglia from Alzheimer's disease models and human brains, linking chromatin remodeling to mitochondrial immune activation.
- KAT7 activates transcription of Cmpk2, a mitochondrial kinase essential for mtDNA synthesis, thereby promoting mtDNA release and driving cGAS-STING and NLRP3 inflammatory signaling.
- Loss or inhibition of KAT7 reduces Cmpk2 expression, impairs mtDNA replication and release, and suppresses neuroinflammatory pathways.
- Microglia-specific deletion or pharmacological inhibition of KAT7 mitigates neuroinflammation, decreases β-amyloid burden, restores synaptic plasticity, and improves cognitive function in Alzheimer's disease mouse models.
- The findings establish an epigenetic-mitochondrial axis in microglia as a key driver of Alzheimer's pathogenesis and identify KAT7 as a potential therapeutic target.