BNIP1 inhibits the fusion of autophagosome and lysosome in hippocampal neurons and promotes the development of Alzheimer's disease

Author:

Li Chen1,Zhang Miao1,Xia Hongyan1,Zhi Xiaoyan1,Wang Ning1,Long Yaolin1,Yuan Yuan1,Shen YanJun1,Wang Li1,Wang Xiaohui1

Affiliation:

1. Shanxi Medical University

Abstract

Abstract

Background BNIP1 (BCL2 interacting protein 1) is a soluble N-ethyl maleimide sensitive factor attachment protein receptor, and its decreased expression is potentially associated with the occurrence and development of Alzheimer's disease (AD), and the regulation of BNIP1 has potential significance for the prevention and treatment of AD. Methods The expression of BNIP1 protein was detected in APP/PS1 transgenic mice and APP-overexpressed HT22 hippocampal nerve cells. The most relevant protein components of BNIP1 expression were investigated by mass spectrometry. After using small interfering RNA and plasmid to regulate the expression of BNIP1, the detection results were strengthened to ensure the accuracy and reliability of the experiment. Results In our study, we detected that the decrease of BNIP1 protein in APP/PS1 double-transgenic mice and APP-overexpressed HT22 hippocampal nerve cells inhibited the fusion of autophagosome and lysosome, and further induced the decrease of Rab7 protein in Rab5b recruitment. Overexpression of BNIP1 can promote the fusion of autophagosome and lysosome. The knockdown of BNIP1 resulted in further dysfunction of autophagosome and lysosome fusion of APP-overexpressed HT22 hippocampal nerve cells. Conclusions These results suggest that the decrease of BNIP1 can lead to the dysfusion of AD autophagosome and lysosome, while overexpression of BNIP1 can ultimately promote the fusion of AD autophagosome and lysosome by inducing Rab5b to recruit Rab7, which provides a potential intervention target for the treatment of AD.

Publisher

Research Square Platform LLC

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