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摘要
Aim: The proteolytic cleavage of Tau is involved in A beta-induced neuronal dysfunction and cell death. In this study, we investigated whether atorvastatin could prevent Tau cleavage and hence prevent A beta(1-42) oligomer (A beta O)-induced neurotoxicity in cultured cortical neurons. Methods: Cultured rat hippocampal neurons were incubated in the presence of A beta Os (1.25 mu mol/L) with or without atorvastatin pretreatment. ATP content and LDH in the culture medium were measured to assess the neuronal viability. Caspase-3/7 and calpain protease activities were detected. The levels of phospho-Akt, phospho-Erk1/2, phospho-GSK3 beta, p35 and Tau proteins were measured using Western blotting. Results: Treatment of the neurons with A beta O significantly decreased the neuronal viability, induced rapid activation of calpain and caspase-3/7 proteases, accompanied by Tau degradation and relatively stable fragments generated in the neurons. A beta O also suppressed Akt and Erk1/2 kinase activity, while increased GSK3 beta and Cdk5 activity in the neurons. Pretreatment with atorvastatin (0.5, 1, 2.5 mu mol/L) dose-dependently inhibited A beta O-induced activation of calpain and caspase-3/7 proteases, and effectively diminished the generation of Tau fragments, attenuated synaptic damage and increased neuronal survival. Atorvastatin pretreatment also prevented A beta O-induced decreases in Akt and Erk1/2 kinase activity and the increases in GSK3 beta and Cdk5 kinase activity. Conclusion: Atorvastatin prevents A beta O-induced neurotoxicity in cultured rat hippocampal neurons by inhibiting calpain-and caspase-mediated Tau cleavage.
- 出版日期2015-5
- 单位锦州医科大学
