Resveratrol: A Therapeutic Approach to Neurodegenerative Diseases and Aging

Pallas      M.; Canudas      A.M.; Junyent      F.; Jimenez      A.; Verdaguer      E.; Camins      A.

doi:10.2174/157019310792246391

Abstract

Resveratrol (3,5,4-trihydroxystilbene) is a polyphenol present in black grapes and its derivatives. Several reports have shown that resveratrol can prevent or slow the progression of a wide variety of illnesses, including cancer, cardiovascular disease and ischemic injuries as well as enhances stress resistance and extends the lifespan of various organisms from yeast to mammals. The mechanism by which resveratrol exerts such a range of beneficial effects across species and disease models is not yet clear, although at the beginning it was proposed that the antioxidant properties of this drug may explain the majority of its beneficial effects. Another mechanism by which resveratrol could combat tumour formation is induction of cell cycle arrest and apoptosis. The last protective mechanism related with resveratrol is its role as activator of sirtuin 1. Resveratrol increases the affinity of sirtuin 1 for its acetylated substrates, possibly inducing a conformational change of the enzyme. The axis sirtuin 1/PGC-1 activated by the resveratrol is a signalling pathway involved in several cellular contexts and tissues, each of the actors involved may promote a separate slow down in the neurodegenerative process. This neuroprotective action is very likely due the fact that the central factor of this signal, PGC-1, promotes mitochondrial activity while neurodegenerative diseases are linked to mitochondrial failures. It is strongly suggested that the activation of the axis sirtuin 1 /PGC-1 by resveratrol could be a key feature of the mechanisms of neuroprotection by this polyphenol and give birth to new therapeutic prospects.

Keywords: Oxidative stress, cell cycle, sirtuin 1

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