title: Neuroprotective and metabolic effects of resveratrol: therapeutic implications for Huntington's disease and other neurodegenerative disorders.
abstract: Resveratrol is a naturally occurring polyphenolic compound associated with beneficial effects on aging, metabolic disorders, inflammation and cancer in animal models and resveratrol is currently being tested in numerous clinical trials. Resveratrol may exert these effects by targeting several key metabolic sensor/effector proteins, such as AMPK, SIRT1, and PGC-1α. Resveratrol has also received considerable attention recently for its potential neuroprotective effects in neurodegenerative disorders where AMPK, SIRT1 or PGC-1α may represent promising therapeutic targets. A recent study published in Experimental Neurology (Ho et al., 2010) examined the therapeutic potential of a micronised proprietary resveratrol formulation, SRT501 in the N171-82Q transgenic mouse model of Huntington's disease (HD). HD is a progressive and devastating genetic neurodegenerative disorder that is associated with downregulation of PGC-1α activity. The Ho et al. study found that SRT501 treatment did not lead to significant improvement in weight loss, motor performance, survival and striatal atrophy. However, other studies have reported neuroprotective effects of resveratrol and a distantly related polyphenol, fisetin, in HD models. HD has been associated with diabetes mellitus. Interestingly, evidence from the Ho et al. study suggests a resveratrol formulation induced beneficial anti-diabetic effect in N171-82Q mice. This commentary summarizes the pertinent outcomes from the Ho et al. study and discusses the further prospects of resveratrol and other polyphenols, including novel grape-derived polyphenols, in the treatment of HD and other neurodegenerative disorders.
authors: Center of Excellence for Research in Complementary and Alternative Medicine in Alzheimer's Disease, Department of Neurology, Mount Sinai School of Medicine, 1498 Madison Avenue, New York, NY 10029, USA. giulio.pasinetti@mssm.edu
authors: Giulio Maria
authors: GM
authors: Pasinetti
authors: Jun
authors: J
authors: Wang
authors: Philippe
authors: P
authors: Marambaud
authors: Mario
authors: M
authors: Ferruzzi
authors: Paul
authors: P
authors: Gregor
authors: Lindsay Alexis
authors: LA
authors: Knable
authors: Lap
authors: L
authors: Ho
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000188:drug therapy* / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D013267:Stilbenes