Neuron-derived mitochondrial DNA (mtDNA) activates microglia via the Z-DNA binding protein 1 (ZBP1)-mediated pathway in mild traumatic brain injury - PubMed
19 hours ago
- #mtDNA signaling
- #microglial activation
- #neuroinflammation
- Neuron-derived mitochondrial DNA (mtDNA) activates microglia through the Z-DNA binding protein 1 (ZBP1) pathway in mild traumatic brain injury (mTBI).
- In mTBI, neuronal mtDNA is damaged and released via extracellular vesicles, triggering microglial activation by binding to ZBP1, which activates the ZBP1-TBK1-IRF3 pathway, leading to inflammatory cytokine expression.
- ZBP1 knockout mice showed suppressed microglial activation in acute mTBI, but this exacerbated hippocampal-related memory deficits in the postacute phase, highlighting the role of mtDNA-ZBP1 signaling in neuroinflammation and cognitive outcomes.