Cai Zhiyou, Zhou Yingjun, Liu Zhou, Ke Zunyu, Zhao Bin
Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei Province, People's Republic of China.
Department of Neurology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang, Gangdong Province, People's Republic of China ; Institute of Neurology, Gangdong Medical College, Zhanjiang, Gangdong Province, People's Republic of China.
Neuropsychiatr Dis Treat. 2015 Aug 17;11:2091-9. doi: 10.2147/NDT.S84755. eCollection 2015.
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.
大量研究表明，自噬功能障碍在阿尔茨海默病的发病机制中起关键作用，包括β-淀粉样蛋白（Aβ）表达增加和Aβ清除功能障碍。为了进一步评估自噬在阿尔茨海默病中的作用，本研究旨在探讨自噬对α-分泌酶、β-分泌酶或γ-分泌酶的影响，并观察自噬对自噬清除标志物的影响。这些结果表明，自噬抑制剂和诱导剂均增强了α-、β-和γ-分泌酶的活性以及Aβ的产生。与自噬诱导剂相比，自噬抑制剂可能更能激活γ-分泌酶并促进Aβ的产生和积累。自噬抑制剂和诱导剂对Aβ清除均无影响。因此，自噬抑制剂可能激活γ-分泌酶并促进Aβ的产生和积累，但对Aβ清除无影响。
