Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease.
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.
Karuppagounder
Saravanan S
SS
Department of Neurology and Neurosciences, Weill Medical College of Cornell University, Burke Medical Research Institute, 785 Mamaroneck Ave., White Plains, NY 10605, United States.
Pinto
John T
JT
Xu
Hui
H
Chen
Huan-Lian
HL
Beal
M Flint
MF
Gibson
Gary E
GE
D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D000975:Antioxidants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000378:metabolism; D052160:Benzothiazoles; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002552:Cerebral Ventricles / Q000473:pathology; D003545:Cysteine / Q000378:metabolism; D019587:Dietary Supplements; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000235:genetics* / Q000473:pathology*; D000077185:Resveratrol; D056564:Sirtuin 1; D037761:Sirtuins / Q000378:metabolism; D013267:Stilbenes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013844:Thiazoles; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
D000975:Antioxidants; D052160:Benzothiazoles; D013267:Stilbenes; D013844:Thiazoles; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D016875:tau Proteins; C009462:thioflavin T; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins; D005978:Glutathione; D003545:Cysteine; D001205:Ascorbic Acid; D000077185:Resveratrol