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

Abstract

Zhiyou Cai,1 Yingjun Zhou,1 Zhou Liu,2,3 Zunyu Ke,1 Bin Zhao2,3 1Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei Province, 2Department of Neurology, The Affiliated Hospital of Guangdong Medical College, 3Institute of Neurology, Guangdong Medical College, Zhanjiang, Guangdong Province, People’s Republic of China Abstract: Numerous studies have shown that autophagy failure plays a critical role in the pathogenesis of Alzheimer’s disease, including increased expression of beta-amyloid (Aβ) protein and the dysfunction of Aβ clearance. To further evaluate the role of autophagy in Alzheimer’s disease, the present study was implemented to investigate the effects of autophagy on α-secretase, β-secretase, or γ-secretase, and observe the effects of autophagy on autophagic clearance markers. These results showed that both autophagy inhibitor and inducer enhanced the activity of α-, β-, and γ-secretases, and Aβ production. Autophagy inhibitor may more activate γ-secretase and promote Aβ production and accumulation than its inducer. Both autophagy inhibitor and inducer had no influence on Aβ clearance. Hence, autophagy inhibitor may activate γ-secretase and promote Aβ production and accumulation, but has no influence on Aβ clearance. Keywords: Alzheimer’s disease, autophagy, beta-amyloid, secretases