Microglial OTUD6A promotes neuroinflammation and Alzheimer's disease pathogenesis by deubiquitinating C/EBPβ - PubMed
3 hours ago
- #Neuroinflammation
- #Alzheimer's Disease
- #Microglia
- Microglial OTUD6A is upregulated in Alzheimer's disease (AD) models and promotes neuroinflammation.
- OTUD6A deubiquitinates C/EBPβ at lysine 253, stabilizing it and enhancing NF-κB signaling and cytokine production.
- Knockout or knockdown of Otud6a reduces cognitive deficits and neuroinflammation in AD mice.
- The catalytic activity of OTUD6A (residue C157A) is essential for its role in C/EBPβ stabilization.
- C/EBPβ knockdown reverses OTUD6A-mediated neuroinflammation, confirming the OTUD6A-C/EBPβ-NF-κB axis in AD pathogenesis.
- Targeting OTUD6A may offer a therapeutic strategy to mitigate neuroinflammation in Alzheimer's disease.