Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease

被引:381
作者
Karuppagounder, Saravanan S. [1 ]
Pinto, John T. [2 ]
Xu, Hui [1 ]
Chen, Huan-Lian [1 ]
Beal, M. Flint [3 ]
Gibson, Gary E. [1 ]
机构
[1] Cornell Univ, Dept Neurol & Neurosci, Weill Med Coll, Burke Med Res Inst, White Plains, NY 10605 USA
[2] New York Med Coll, Dept Biochem & Mol Biol, Valhalla, NY 10595 USA
[3] Cornell Univ, Dept Neurol & Neurosci, Weill Med Coll, New York, NY 10021 USA
关键词
Oxidative stress; Mitochondria; Alzheimer's disease; A beta peptide; Stilbenes; APOLIPOPROTEIN-E GENOTYPE; OXIDATIVE STRESS; AMINO-ACIDS; ANTIOXIDANT ACTIVITY; NEUROBLASTOMA-CELLS; LIPID-PEROXIDATION; LDL OXIDATION; RED WINE; BRAIN; MICE;
D O I
10.1016/j.neuint.2008.10.008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Resveratrol, a polyphenol found in red wine, peanuts, soy beans, and pomegranates, possesses a wide range of biological effects. Since resveratrol's properties seem ideal for treating neurodegenerative diseases, its ability to diminish amyloid plaques was tested. Mice were fed clinically feasible dosages of resveratrol for forty-five days. Neither resveratrol nor its conjugated metabolites were detectable in brain. Nevertheless, resveratrol diminished plaque formation in a region specific manner. The largest reductions in the percent area occupied by plaques were observed in medial cortex (-48%), striatum (-89%) and hypothalamus (-90%). The changes occurred without detectable activation of SIRT-1 or alterations in APP processing. However, brain glutathione declined 21% and brain cysteine increased 54%. The increased cysteine and decreased glutathione may be linked to the diminished plaque formation. This study supports the concept that onset of neurodegenerative disease may be delayed or mitigated with use of dietary chemo-preventive agents that protect against beta-amyloid plaque formation and oxidative stress. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:111 / 118
页数:8
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