Nutraceuticals in CNS diseases: Potential mechanisms of neuroprotection

In recent years, there has been increasing attention devoted to the possibility that several nutraceuticals may act as neuroprotective agents. Such protective effects have often been ascribed to a direct antioxidant effect; however, the exact mechanisms of neuroprotection remain elusive, and alternate mechanisms have been proposed. This chapter focuses on some examples of potential mechanisms of neuroprotection at the cellular, biochemical, and molecular level. Polyphenols (particularly quercetin) are discussed as model nutraceuticals, although other molecules are mentioned and discussed to illustrate additional potential neuroprotective mechanisms. Quercetin neuroprotection may be ascribed to its direct antioxidant ability; however, it is more likely that it acts in a hormetic fashion, stimulating cellular defenses by activating the Nrf2-ARE pathway. Induction of the antioxidant/anti-inflammatory enzyme paraoxonase 2 may represent an additional novel mechanism of neuroprotection. Interference with multiple signal transduction pathways, activation of sirtuins (SIRT1), and modulation of autophagy are other mechanisms that nutraceuticals may use to provide beneficial effects in central nervous system diseases.