Abstract
Alzheimer’s disease (AD) is an age-related and progressive neurodegenerative disease. Beta-amyloid (Aβ) plays an important role in the pathogenesis of AD. Autophagy is a self-degradative process and its related protein Beclin-1 is involved in the initiation of autophagy. However, the role of Beclin-1 in the pathogenesis of AD is rarely reported. In this study, we examined cell viability and medium levels of neuron-specific enolase (NSE) in PC12 cells incubated with gradient concentrations of Aβ1-42 (0.625, 1.25, 2.5, 5, 10 μM) for 6, 12, 24, 48, and 72 h, drew the index changes curves, and investigated the correlation between them. The result showed that cell viability was negatively correlated with NSE levels. Based on this study, Beclin-1 expression was quantitatively detected in Aβ1-42-treated PC12 cells and the dynamic changes curve of Beclin-1 was drawn from 3 to 72 h. Beclin-1 expression was positively correlated with cell viability. Furthermore, both autophagy inhibitor 3-methyladenine (3-MA) and autophagy activator rapamycin were used to investigate the effect of autophagy on Aβ1-42-induced cell injury. Aβ1-42-induced Beclin-1 expression was further upregulated by rapamycin but was downregulated by 3-MA. Moreover, cell viability was increased by rapamycin but was decreased by 3-MA, and NSE was decreased by rapamycin but was increased by 3-MA, suggesting that activation of Beclin-1-dependent autophagy before the damage occurred can prevent neuronal cell death, while inhibition of Beclin-1-dependent autophagy can hastened cell death. These findings indicate that increasing Beclin-1-dependent autophagy may have a preventive effect before the AD occurred.
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This work was supported by the Guangdong Natural Science Foundation of China (no. S2012010010625). We would like to express our sincere thanks to the reviewers and editors for the constructive and positive comments.
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Xue, Z., Zhang, S., Huang, L. et al. Upexpression of Beclin-1-Dependent Autophagy Protects Against Beta-amyloid-Induced Cell Injury in PC12 Cells. J Mol Neurosci 51, 180–186 (2013). https://doi.org/10.1007/s12031-013-9974-y
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DOI: https://doi.org/10.1007/s12031-013-9974-y