Epigallocatechin Gallate Attenuates Beta-Amyloid Generation And Oxidative Stress Involvement Of Ppar Gamma In N2a/App695 Cells
NEUROCHEMICAL RESEARCH(2017)
摘要
The accumulation of beta-amyloid (A beta) peptide plaques is a major pathogenic event in Alzheimer's disease (AD). A beta is a cleaved fragment of APP via BACE1, which is the rate-limiting enzyme in APP processing and A beta generation. Nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) is considered to be a potential target for AD treatment, because of its potent antioxidant and inhibitory effects on A beta production by negatively regulating BACE1. Epigallocatechin gallate (EGCG), a highly active catechin found in green tea, is known to enhance metabolic activity and cognitive ability in the mice model of AD. To investigate whether the therapeutic effect of EGCG is related to the PPAR gamma pathway, we analysed the alterations in the intracellular molecular expression of PPAR gamma after EGCG treatment in the N2a/APP695 cell line. In this study, we observed that EGCG attenuated A beta generation in N2a/APP695 cells, such as the PPAR gamma agonist, pioglitazone, by suppressing the transcription and translation of BACE1 and that its effect was attenuated by the PPAR gamma inhibitor, GW9662. Intriguingly, EGCG significantly reinforced the activity of PPAR gamma by promoting its mRNA and protein expressions in N2a/APP695 cells. Moreover, EGCG also decreased the expression of pro-apoptotic proteins (Bax, caspase-3), reduced the activity of the anti-inflammatory agent NF-kappa B and inhibited the oxidative stress by decreasing the levels of ROS and MDA and increasing the expression of MnSOD. Co-administration of GW9662 also significantly decreased the EGCG-mediated neuroprotective effect evidenced by the increase in oxidative stress and inflammatory markers. The therapeutic efficacy of EGCG in AD may be derived from the up-regulation of PPAR gamma mRNA and protein expressions.
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关键词
Alzheimer's disease (AD),Epigallocatechin gallate (EGCG),beta-Amyloid,PPAR gamma,BACE1
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