Autophagy dysfunction upregulates beta-amyloid peptides via enhancing the activity of γ-secretase complex

Abstract

Numerous studies have shown that autophagy failure plays a critical role in thpathogenesis of Alzheimer’s disease, including increased expression of beta-amyloid (Aß) proteiand the dysfunction of Aß clearance. To further evaluate the role of autophagy in Alzheimer’disease, the present study was implemented to investigate the effects of autophagy on α-secretaseß-secretase, or γ-secretase, and observe the effects of autophagy on autophagic clearance markersThese results showed that both autophagy inhibitor and inducer enhanced the activity of α-, ß-, anγ-secretases, and Aß production. Autophagy inhibitor may more activate γ-secretase and promotAß production and accumulation than its inducer. Both autophagy inhibitor and inducer had ninfluence on Aß clearance. Hence, autophagy inhibitor may activate γ-secretase and promotAß production and accumulation, but has no influence on Aß clearance.