The role of microglial PARP-1 in Alzheimer’s disease
Rezaeian Mehrabadi, Abbas
Alzheimer’s disease (AD) is a neurodegenerative disorder with profound chronic neuroinflammation. Our previous studies have identified poly(ADP-ribose) polymerase-1 (PARP-1) as a key driver of microglial pro-inflammatory functions. Here we tested a hypothesis that microglial PARP-1-mediated pro-inflammatory activation can affect AD disease progression (in vivo) and directly disrupt blood-brain barrier integrity (in vitro). The cognitive functions in AD and WT mice were assessed by behavioral test. The brain tissue was analyzed by immunocytochemistry and cultured endothelial cells were analyzed for tight junction proteins expression and permeability assays. Microglial constitutive PARP-1 activation induced cognitive impairments in WT and AD mice, changed microglial morphology, increased their number and intensity and induced astrogliosis. NO and TNFα that released by Aβ-induced microglia reduced the expression of tight junction proteins and increased paracellular permeability in endothelial cells. In Conclusion, our data demonstrate that microglial continuous PARP-1 activation can directly drive AD pathology and progression.
Alzheimer' Disease, Microglia, PARP-1