Role of Nrf2-dependent ARE-driven antioxidant pathway in neuroprotection

The promoter regions of many detoxification enzymes contain a cis-acting enhancer known as the antioxidant response element (ARE). NF-E2-related factor 2 (Nrf2) is considered as one of the major transcription factors for the ARE. Nrf2-dependent transcriptional activation by means of the ARE is known to coordinate the upregulation of these antioxidant enzymes involved in combating oxidative stress and has been shown to be protective against neural toxicants. The mitochondrial complex II inhibitor malonate causes striatal damage reminiscent of Huntington's disease and is known to involve oxidative stress in its pathogenesis. In order to achieve a systemic upregulation of antioxidant potential in local striatal region, a cell-based, Nrf2-dependent antioxidant gene therapy is performed to attenuate malonate-induced neuronal cell death. The details for generating Nrf2-overexpressing astrocytes and grafting them onto the lesion model are described in this chapter.