CHIP modulates APP-induced autophagy-dependent pathological symptoms in Drosophila.,Aging Cell

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CHIP modulates APP-induced autophagy-dependent pathological symptoms in Drosophila.
Aging Cell ( IF 8.0 ) Pub Date : 2019-11-28 , DOI: 10.1111/acel.13070
Luming Zhuang ₁ , Fei Peng ₁ , Yuanyuan Huang ₁ , Wenzhe Li ₁ , Jiuhong Huang ₂ , Yunqiang Chu ₁ , Pu Ren ₁ , Ying Sun ₁ , Yan Zhang ₁ , Elleen Xue ₃ , Xiaowei Guo ₁ , Xiafeng Shen ₁ , Lei Xue ₁

Affiliation

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.

中文翻译：

CHIP调节果蝇中APP诱导的自噬依赖性病理症状。

自噬的失调与阿尔茨海默氏病（AD）的神经退行性过程有关，但是自噬是AD的原因还是后果仍存在争议。我们以前曾在果蝇中表达过全长的人类APP，并建立了具有多种AD样症状的果蝇AD模型。在这里，我们报道CHIP的耗竭有效地缓解了APP诱发的病理症状，包括形态，行为和认知缺陷。从机理上讲，APP引起的自噬功能障碍需要CHIP，它通过增加BACE和Psn的表达来促进Aβ的产生。。我们的发现表明异常的自噬不仅是APP活动异常的结果，而且还导致APP代谢失调和随后的AD发病机制。

更新日期：2019-11-28

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