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Overexpression of NF-E2 related factor 2 via viral-mediated gene transfer in vivo. Imbeault, Sophie

Abstract

The transcription factor NF-E2 related factor 2 (Nrf2) is responsible for the upregulation of the cellular anti-oxidant defence system. Upon stimulation by free radicals or reactive oxygen species (ROS), the cytoplasmic-bound Nrf2 translocates to the nucleus and initiates transcription of genes containing anti-oxidant response elements (AREs) within their promoter region. Many ARE-containing genes contribute to the maintenance of redox homeostasis within the cell thus promoting cell survival. To date, limited work has been done looking at Nrf2-mediated neuroprotection in vivo. Here, we use viral-mediated gene delivery via stereotaxic injection into the adult Wistar rat brain in order to overexpress Nrf2. We exploit the capacity of 3-nitropropionic acid (3-NP) to produce ROS in order to provide an oxidative challenge to our animals. Histological analyses show reduced lesion size (lesions are ∼55 % smaller than controls, p

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