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The Role of Nonneuronal Nrf2 Pathway in Ischemic Stroke: Damage Control and Potential Tissue Repair

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Non-Neuronal Mechanisms of Brain Damage and Repair After Stroke

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

Abstract

Nuclear factor erythroid 2-related factor (Nrf2) is a transcription factor that controls the expression of predominant antioxidant system in the central nervous system (CNS). Under normal conditions, Nrf2 is sequestered by Keap1 and degenerated by the ubiquitin system. Oxidative stress initiates Nrf2 nuclear translocation, leading to expression of antioxidant molecules and enzymes. In stroke, oxidative stress is one of the major causes of neuronal death, and Nrf2 pathway is activated in both in vitro and in vivo ischemic models. In addition to mediate self-defense in neurons, Nrf2 also actively regulates the expression of cytoprotective enzymes in other cell types within the neurovascular unit (NVU), including astrocytes and endothelial cells, and thus supports neuronal function and survival through cell–cell interaction. The roles of microglias in stroke are still controversial, but close to be clarified. In this chapter, we will briefly introduce Nrf2 pathway, followed by its key roles of nonneuronal Nrf2 in limiting ischemic injury and emerging roles in brain tissue repair after stroke.

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Authors and Affiliations

  1. Department of Neurology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA, 15213, USA

    Tuo Yang M.D., Yang Sun M.D. & Feng Zhang M.D., Ph.D.

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  1. Tuo Yang M.D.
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  2. Yang Sun M.D.
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  3. Feng Zhang M.D., Ph.D.
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Correspondence to Feng Zhang M.D., Ph.D. .

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  1. Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Jun Chen

  2. Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    John H. Zhang

  3. Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, California, USA

    Xiaoming Hu

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Yang, T., Sun, Y., Zhang, F. (2016). The Role of Nonneuronal Nrf2 Pathway in Ischemic Stroke: Damage Control and Potential Tissue Repair. In: Chen, J., Zhang, J., Hu, X. (eds) Non-Neuronal Mechanisms of Brain Damage and Repair After Stroke. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-319-32337-4_18

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