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. (2020). CHIP modulates APP-induced autophagy-dependent pathological symptoms in Drosophila. Aging Cell 19(2): e13070.
FlyBase ID
FBrf0244737
Publication Type
Research paper
Abstract
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 in Drosophila and established a fly AD model that exhibits multiple AD-like symptoms. Here we report that depletion of CHIP effectively 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 of BACE and Psn. 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.
