Lige Leng, Ziqi Yuan, Ruiyuan Pan, Xiao Su, Han Wang, Jin Xue, Kai Zhuang, Ju Gao, Zhenlei Chen, Hui Lin, Wenting Xie, Huifang Li, Zhenyi Chen, Keke Ren, Xiao Zhang, Wenting Wang, Zi-Bing Jin, Shengxi Wu, Xinglong Wang, Zengqiang Yuan, Huaxi Xu, Hei-Man Chow, Jie Zhang
Microglial cells consume adenosine triphosphate (ATP) during phagocytosis to clear neurotoxic β-amyloid in Alzheimer's disease (AD). However, the contribution of energy metabolism to microglial function in AD remains unclear. Here, we demonstrate that hexokinase 2 (HK2) is elevated in microglia from an AD mouse model (5xFAD) and AD patients. Genetic deletion or pharmacological inhibition of HK2 significantly promotes microglial phagocytosis, lowers the amyloid plaque burden and attenuates cognitive impairment in male AD mice...
October 2022: Nature metabolism