Biomedical Fast Takes


Resveratrol: Neuroprotector

These days, there aren’t many phytocompounds that have a bigger marquee, lit up in lights, than resveratrol. For many years it has been considered a potential anticancer nutrient, and has been found to have a wide array of applications, not the least of which is its possible life extension benefits. Recently, continuing research has extended its use into the realm of neuroscience, where it has been found to display neuroprotective actions.1 Not unrelated, resveratrol activates the sirtuins’ family member SIRT1. Sirtuins are enzymes with preferential deacetylase activity, a mechanism by which sirtuins interfere in a positive way with certain transcription machineries.

Human sirtuins are coded by seven genes, the most investigated of which SIRT1, which is involved in a number of physiologic and pathologic processes including apoptosis, autophagy, diabetes, cancer, cardiovascular disorders, and neurodegeneration. In vitro and in vivo, resveratrol shows neuroprotective features in models of Alzheimer’s disease, and it has proved to be beneficial also in Parkinson’s disease, Huntington’s disease, ischemic stroke, and epilepsy.

Parkinson’s, the second most common neurodegenerative disease, is characterized by a progressive loss of dopamine neurons in the substantia nigra. Mounting evidence indicates that inhibition of microglia-mediated neuroinflammation may become a reliable protective strategy for this disease. Resveratrol, a polyphenol found in red wine and grapes, is known to possess antioxidant, anticancer, and antiinflammatory properties. Although it has been shown that resveratrol offers neuroprotective effects against neurodegenerative disorders, ischemia, and seizure, the mechanisms causing its beneficial effects on dopamine decline are not well understood.

In a new study study, rat primary midbrain neuron-glia cultures were used to clarify the molecular mechanisms of resveratrol to offer neuroprotection.2 The results clearly demonstrated that resveratrol protected dopamine neurons against induced neurotoxicity in both concentration- and time-dependent ways. Furthermore, it worked by inhibiting microglial activation and reducing proinflammatory factor release that this caused.

Of interest, especially to long time students of resveratrol, neuroprotection was correlated to the inhibition of NADPH oxidase. NADPH stands for nicotinamide adenine dinucleotide phosphate, a major niacin-containing redox-active “electron storage” compound and a major source of superoxide radicals. In the study, resveratrol reduced NADPH oxidase-generated reactive oxygen species. At the same time, resveratrol attenuated NADPH oxidase damage to the cell membrane. And finally, and first in importance, resveratrol did not protect the neurons in cultures from NADPH oxidase-deficient mice. Altogether, this study suggests that resveratrol protects dopamine, and that NADPH oxidase may be a major player in the mechanism by which it works as a neuroprotector.

References

  1. Albani D, Polito L, Signorini A, Forloni G. Neuroprotective properties of resveratrol in different neurodegenerative disorders. Biofactors 2010 Sep 16. [Epub ahead of print]
  2. Zhang F, Shi JS, Zhou H, Wilson B, Hong JS, Gao HM. Resveratrol protects dopamine neurons against lipopolysaccharide-induced neurotoxicity through its anti-inflammatory actions. Mol Pharmacol 2010 Sep 1;78(3):466-77.

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