Abstract
Studies have shown that misfolded proteins and endoplasmic reticulum (ER) stress play pivotal roles in the progression of Alzheimer's disease (AD). It has also been reported that ER stress is considered to be a common mediator of apoptosis in neurodegenerative disorders like AD. However, the precise mechanisms leading to neuronal cell death caused by ER stress in AD remain unclear. Hsp70, the major inducible form of the heat shock protein family, functions at the level of chaperone-mediated protein folding. Enhanced expression of Hsp70 suppresses the neurotoxicity caused by protein misfolding. EGb761, an accepted traditional Chinese medicine used to treat AD, was used here to examine the molecular mechanism underlying its protective effect on ER stress and Hsp70. Our study shows that pretreatment with EGb761 overcomes the neurotoxicity of the Aβ1-42 oligomer by increasing Hsp70, Grp78, IRE1α and pAkt expression in a dose-dependent manner and significantly decreases cell apoptosis-related protein expression. Our findings suggest that the neuroprotective effect of EGb761 is related to ER stress activation and increased Hsp70 expression, and subsequent activation of Akt. However, the effect of EGb761 on these processes is not direct.
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