Longevity & AgingMitochondrial Molecules Drive Brain Inflammation in Neurodegeneration
This comprehensive review examines how molecules released from damaged mitochondria — including ATP, cytochrome c, mitochondrial DNA, and metabolites like succinate — act as danger signals that activate microglia and astrocytes in the brain. Called mitochondrial damage-associated molecular patterns (mtDAMPs), these molecules bind pattern recognition receptors on glial cells, triggering inflammatory cascades linked to Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. The authors catalog ten distinct mtDAMPs, map their receptors and signaling pathways, and highlight where CNS-specific evidence is strong versus where critical research gaps remain. They identify the shortage of human cell and tissue studies as a key limitation, and argue that targeting mtDAMP-receptor interactions could yield novel therapies for currently untreatable neurodegenerative conditions.
