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

Z Cai, Y Zhou, Z Liu, Z Ke, B Zhao�- Neuropsychiatric disease and�…, 2015 - Taylor & Francis
Z Cai, Y Zhou, Z Liu, Z Ke, B Zhao
Neuropsychiatric disease and treatment, 2015Taylor & Francis
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�…
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.
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