trans-Resveratrol as a neuroprotectant

Abstract

Epidemiological evidence indicates that nutritionally-derived polyphenols such as resveratrol (RES) have neuroprotective properties. Administration of RES to culture media protects a wide variety of neuronal cell types from stress-induced death. Dietary supplementation of RES can ameliorate neuronal damage and death resulting from both acute and chronic stresses in rodents. The specific molecular mechanisms by which RES acts at the cellular level remain incompletely understood. However, many experimental data indicate that RES reduces or prevents the occurrence of oxidative damage. Here we discuss possible mechanisms by which RES might exert protection against oxidative damage and cell death. Evidence suggesting that RES's chemical antioxidant potential is not sufficient explanation for its effects is discussed. Putative biological activities, including interactions with estrogen receptors and sirtuins are critically discussed. We provide a synthesis of how RES's phytoestrogenic properties might mediate the neuronal stress resistance underlying its observed neuroprotective properties.

Figure 1

A proposed pathway for the RES-induced stimulation of MnSOD transcription via estrogen receptor-mediated regulation of NFκB activity. Based on the E2-induced transcriptional upregulation of MnSOD and other mitochondrial proteins described by Borras et al. [63]. MAPK = mitogen activated protein kinase; ERK1/2 = extracellular signal regulated kinases ½; NFκB = nuclear factor κB; MnSOD = manganese superoxide dismutase.