Role of Astrocytic Dysfunction in the Pathogenesis of Parkinson’s Disease Animal Models from a Molecular Signaling Perspective

Figure 4

The Nrf2-ARE signaling pathway in Parkinson’s disease. Under unstressed conditions, oxidative molecules like ROS and RNS activate the protective antioxidant pathway, dissociating the cytosolic Nrf2/Keap1 complex. The Nrf2 factor translocates to the nucleus where associated with bZip proteins trigger the expression of several homeostatic genes with the ARE sequence in their promoters, including SOD, HO-1, GST, and NQO1. Upon inactivation, Nrf2 is sequestered by Keap1 and targeted for ubiquitination and proteasomal degradation. Nrf2: nuclear factor (erythroid-derived 2)-related factor 2; Keap1: Kelch-like ECH-associated protein 1; bZip: basic region leucine zipper (bZip) transcription factors; SOD: superoxide dismutase; HO-1: heme oxygenase-1; GST: glutathione S-transferase; NQO1: NAD(P)H: quinone oxidoreductase-1.