Overexpression of SHP1 blocks BACE1 degradation through autophagy and induces ROS in the Alzheimer\'s disease

• 1、Institute of Neuroscience Soochow University, Suzhou 215000

Abstract：Recent studies have indicated SHP1(Src homology region 2 domain-containing phosphatase-1) play an important role in autophagosome biogenesis. Further, defects in autophagy are likely to contribute to the neurodegenerative processes in numerous diseases, including Alzheimer\'s disease (AD). However, the role of SHP1 in the AD is rarely reported. Here, our study indicates that compared with normal mice and cells, the SHP1 is increased in APP/PS1 transgenic mice and HEK-APP cells. We show that SHP1, BACE1, andLC3 can form a complex compound. Overexpression of SHP1 increases the level of reactive oxygen species (ROS) and causes autophagy dysfunction. We further demonstrate that overexpression of SHP1 protein inhibits BACE1 protein degradation through autophagy. Thus, these results indicate SHP1 may be a potential risk factor in Alzheimer\'s disease.

Keywords： Neurobiology BACE1 SHP1 Autophagy