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Oxidative Medicine and Cellular Longevity
Volume 2016, Article ID 2986796, 10 pages
Review Article

Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More

1Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA
2Department of Neuroscience, University of Parma Medical School, 43100 Parma, Italy

Received 27 November 2015; Revised 4 January 2016; Accepted 6 January 2016

Academic Editor: Felipe Dal Pizzol

Copyright © 2016 Lucio G. Costa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Increasing interest has recently focused on determining whether several natural compounds, collectively referred to as nutraceuticals, may exert neuroprotective actions in the developing, adult, and aging nervous system. Quercetin, a polyphenol widely present in nature, has received the most attention in this regard. Several studies in vitro, in experimental animals and in humans, have provided supportive evidence for neuroprotective effects of quercetin, either against neurotoxic chemicals or in various models of neuronal injury and neurodegenerative diseases. The exact mechanisms of such protective effects remain elusive, though many hypotheses have been formulated. In addition to a possible direct antioxidant effect, quercetin may also act by stimulating cellular defenses against oxidative stress. Two such pathways include the induction of Nrf2-ARE and induction of the antioxidant/anti-inflammatory enzyme paraoxonase 2 (PON2). In addition, quercetin has been shown to activate sirtuins (SIRT1), to induce autophagy, and to act as a phytoestrogen, all mechanisms by which quercetin may provide its neuroprotection.