科研之友
微信
新浪微博
Facebook
分享链接
摘要
Neuritic plaque is the pathological hallmark in Alzheimer's disease (AD). Amyloid- protein (A), the central component of neuritic plaques, is generated from amyloid- precursor protein (APP) by -site APP cleaving enzyme1 (BACE1) and -secretase. -site APP cleaving enzyme2 (BACE2), a homolog of BACE1, functions differently from BACE1 in APP processing. BACE1 is the -secretase essential for A production, and BACE2, a -secretase, cleaves APP within the A domain, preventing A production. Elucidation of the mechanism underlying BACE2 degradation is important for defining its biological features and its potential role in Alzheimer's disease drug development. In this report we first showed that the half-life of BACE2 is approximately 20h. Lysosomal inhibition increased BACE2 protein levels whereas proteasomal inhibition had no effect on BACE2 protein expression. Furthermore, we identified that macroautophagy mediated BACE2 degradation. Finally, we showed that lysosomal inhibition increased BACE2 cleavage of APP. Taken together, our in vitro study showed that BACE2 is degraded through the macrophagy-lysosome pathway and that lysosomal inhibition affects BACE2 processing of APP. Modulation of BACE2 degradation via the lysosomal pathway could be a new target for AD drug development.
