화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.495, No.1, 12-19, 2018
Overexpression of SNX7 reduces A beta production by enhancing lysosomal degradation of APP
Abnormal production of amyloid-beta peptides (A beta) by proteolytic processing of amyloid precursor protein (APP) is thought to be central to the pathogenesis of Alzheimer's disease (AD). Although many efforts have been made to investigate mechanisms that regulate APP processing, many details remain incompletely understood. Sorting nexins (SNXs) are a family of proteins which are involved in many intracellular trafficking events. Several SNXs have been implicated in APP processing and A beta production. In this study, we extended the investigation to SNX7. We found that overexpression of SNX7 in HEK293T cells reduces the levels of secreted A beta and beta-cleaved N-terminal APP fragments (sAPP beta). Moreover, SNX7 overexpression caused a significant reduction of the steady-state levels of APP as well as of the cell surface APP levels. By using NH4CI and Bafilomycin A1 to inhibit the lysosomal degradative pathway, we found that the reduction of APP induced by SNX7 overexpression was prevented by such inhibition. No change in the cell surface distribution or steady-state levels of BACE1 was detected after overexpression of SNX7. Taken together, these results suggest that SNX7 regulates A beta production by directing APP for degradation. (C) 2017 Elsevier Inc. All rights reserved.