BAD-mediated neuronal apoptosis and neuroinflammation contribute to Alzheimer's disease pathology

著者: 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 - iScience 2021 被引用: 48

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.