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. CHIP modulates APP-induced autophagy-dependent pathological symptoms in Drosophila. Aging Cell. 2019 Nov 28:e13070. PubMed PMID: 31777182.
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."
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