BAD-mediated neuronal apoptosis and neuroinflammation contribute to Alzheimer's disease pathology
Liansheng Zhang, Yun Qian, Jie Li, Xuan Zhou, He Xu, Jie Yan, Jialing Xiang, Xiang Yuan, Beicheng Sun, Sangram S. Sisodia, Yong‐hui Jiang, Xiaohua Cao, Naihe Jing, Anning Lin
Abstract
alleles restores spatial learning and memory deficits in 5XFAD mice. Mechanistically, phosphorylation and inactivation of BAD by neurotropic factor-activated Akt is abrogated in neurons under AD condition. Through reactive oxygen species (ROS)-oxidized mitochondrial DNA (mtDNA) axis, BAD also promotes microglial NLRP3 inflammasome activation, thereby skewing microglia toward neuroinflammatory microglia to inhibit microglial phagocytosis of Aβ in AD mice. Our results support a model in which BAD contributes to AD pathologies by driving neuronal apoptosis and neuroinflammation but suppressing microglial phagocytosis of Aβ, suggesting that BAD is a potential therapeutic target for AD.