Affiliations: Department of Pathophysiology, the Key Laboratory of Neurological Diseases of the Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Correspondence:
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Correspondence to: Xin-Wen Zhou, Department of Pathophysiology, the Key Laboratory of Neurological Diseases of the Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. E-mail: [email protected].
Abstract: Overproduction and accumulation of amyloid-β (Aβ) have been proposed to be an initiating factor of neuron loss in Alzheimer's disease (AD). AKT is a pivotal molecule in regulating neuronal survival, however, it is still not known whether upregulation of AKT can protect the cells from the Aβ-induced apoptosis. By using cell viability assay and flow cytometry, we demonstrated in the present study that overexpression of AKT could significantly attenuate the cell apoptosis induced by Aβ1-42, whereas simultaneous inhibition of PI3 K, the immediate upstream stimulator of AKT, abolished the protective effect of AKT in HEK293 cells. Upregulation of AKT restored the Aβ-induced alterations of the mitochondria-related Bcl-2 family members (including Bcl-xL, Bcl-w, Bad, and Bax) and suppressed the activation of caspase-3 and JNK. Our data suggest that upregulation of AKT could be a promising therapeutic strategy for arresting Aβ toxicity in AD patients.
