Fig. 1
From: Mitochondrial dysfunction in microglia: a novel perspective for pathogenesis of Alzheimer’s disease
Microglial mtDNA in AD. Mitochondria has their unique circular genome called mtDNA. Human mtDNA contains 16,569 base pairs and 37 coding genes, including 22 tRNAs, 2 rRNAs and 13 polypeptides. In AD, microglial mtDNAs are vulnerable to various damages, particularly ROS generated nearby. Damaged mitochondria release abnormal mtDNA to adjacent microglia, which exacerbates inflammatory responses of microglia by triggering TLR and IFN expression and NLRP3 inflammasome activation, amplifying inflammatory effects. Moreover, activated microglia release pro-inflammatory cytokine to neurons, inducing mitochondrial dysfunction and irreversible neuronal damage. Damaged neurons further release mtDNA to microglia, creating a vicious cycle.