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Resveratrol inhibits beta-amyloid-induced neuronal apoptosis through regulation of SIRT1-ROCK1 signaling pathway.

Authors: Feng, X  Liang, N  Zhu, D  Gao, Q  Peng, L  Dong, H  Yue, Q  Liu, H  Bao, L  Zhang, J  Hao, J  Gao, Y  Yu, X  Sun, J 
Citation: Feng X, etal., PLoS One. 2013;8(3):e59888. doi: 10.1371/journal.pone.0059888. Epub 2013 Mar 28.
Pubmed: (View Article at PubMed) PMID:23555824
DOI: Full-text: DOI:10.1371/journal.pone.0059888

Alzheimer's disease (AD) is characterized by the accumulation of beta-amyloid peptide (Abeta) and loss of neurons. Recently, a growing body of evidences have indicated that as a herbal compound naturally derived from grapes, resveratrol modulates the pathophysiology of AD, however, with a largely unclear mechanism. Therefore, we aimed to investigate the protection of resveratrol against the neurotoxicity of beta-amyloid peptide 25-35 (Abeta(25-35)) and further explore its underlying mechanism in the present study. PC12 cells were injuried by Abeta(25-35), and resveratrol at different concentrations was added into the culture medium. We observed that resveratrol increased cell viability through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) colorimetric assays. Flow cytometry indicated the reduction of cell apoptosis by resveratrol. Moreover, resveratrol also stabilized the intercellular Ca(2+) homeostasis and attenuated Abeta(25-35) neurotoxicity. Additionally, Abeta(25-35)-suppressed silent information regulator 1 (SIRT1) activity was significantly reversed by resveratrol, resulting in the downregulation of Rho-associated kinase 1 (ROCK1). Our results clearly revealed that resveratrol significantly protected PC12 cells and inhibited the beta-amyloid-induced cell apoptosis through the upregulation of SIRT1. Moreover, as a downstream signal molecule, ROCK1 was negatively regulated by SIRT1. Taken together, our study demonstrated that SIRT1-ROCK1 pathway played a critical role in the pathomechanism of AD.

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CRRD Object Information
CRRD ID: 10047117
Created: 2015-07-10
Species: All species
Last Modified: 2015-07-10
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.