Sirtuins, brain and cognition: A review of resveratrol effects

Abstract

Sirtuins (SIRTs) are a protein family with high preservation degree among evolutionary scale. SIRTs are histone deacetylases regulatory enzymes of genetic material deeply involved in numerous physiological tasks including metabolism, brain function and aging. Mammals sirtuins comprise seven enzymatic components (SIRT1-SIRT7). The highest studied sirtuin is SIRT1, which plays an essential position in the prevention and evolution of neuro-disorders. Resveratrol (3,5,4-trihydroxystylbene) (RSV) is a polyphenol, which belongs to a family compounds identified as stilbenes, predominantly concentrated in grapes and red wine. RSV is the must studied Sirtuin activator and is used as food supplementary compound. Resveratrol exhibits strong antioxidant activity, reducing free radicals, diminishing quinone-reductase-2 activity and exerting positive regulation of several endogenous enzymes. Resveratrol is also able to inhibit pro-inflammatory factors, reducing the stimulation of the nuclear factor kB (NF-kB) and the release of endogenous cytokines. Resveratrol treatment can modulate multiple signaling pathway effectors related to programmed cell death, cell survival, and synaptic plasticity. In this context, the present review looks over news and the role of Sirtuins activation and resveratrol effects on modulating target genes, cognition and neurodegenerative disorders.

Keywords: Central nervous system; Phytochemistry family; Polyphenol; Sirt; Wine.

Fig. 1

Resveratrol improves cognition through an anti-oxidative mechanism by SIRT1-mediated deacetylation. Unpaired electrons escape the mitochondrial electron transport chain and react with molecular oxygen to produce superoxide, resulting in oxidative stress. Resveratrol acts on SIRT1, which induces ROS detoxifying enzymes that eliminate superoxide.

Fig. 2

SIRT1 is capable of deacetylate p53 in the Lys residues (Lys373 and / or Lys382) and protect multiple cells against Apoptosis induced by DNA damage.