CHIP modulates APP‐induced autophagy‐dependent pathological symptoms in Drosophila
CHIP modulates APP‐induced autophagy‐dependent pathological symptoms in Drosophila
复制标题
CHIP 调节 APP 诱导的果蝇自噬依赖性病理症状
作者：
Zhuang L;Peng F;Huang Y;Li W;Huang J;Chu Y;Ren P;Sun Y;Zhang Y;Xue E;Guo X;Shen X;Xue L
Dysregulation of autophagy is associated with the neurodegenerative processes in Alzheimer's disease (AD), yet it remains controversial whether autophagy is a cause or consequence of AD. We have previously expressed the full‐length human APP inDrosophilaand established a fly AD model that exhibits multiple AD‐like symptoms. Here we report that depletion ofCHIPeffectively palliated APP‐induced pathological symptoms, including morphological, behavioral, and cognitive defects. Mechanistically, CHIP is required for APP‐induced autophagy dysfunction, which promotes Aβ production via increased expression ofBACEandPsn. Our findings suggest that aberrant autophagy is not only a consequence of abnormal APP activity, but also contributes to dysregulated APP metabolism and subsequent AD pathogenesis.
