The Nrf2–ARE cytoprotective pathway in astrocytes

Marcelo R. Vargas; Jeffrey A. Johnson

doi:10.1017/S1462399409001094

The Nrf2–ARE cytoprotective pathway in astrocytes

Published online by Cambridge University Press: 03 June 2009

Marcelo R. Vargas and

Jeffrey A. Johnson

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Marcelo R. Vargas: Affiliation:
Division of Pharmaceutical Sciences, University of Wisconsin, Madison, WI, USA.
Jeffrey A. Johnson*: Affiliation:
Division of Pharmaceutical Sciences, University of Wisconsin, Madison, WI, USA. Waisman Center, Molecular and Environmental Toxicology Center, and Center for Neuroscience, University of Wisconsin, Madison, WI, USA.
*: *Corresponding author: Jeffrey A. Johnson, School of Pharmacy, 6125 Rennebohm Hall, 777 Highland Avenue, University of Wisconsin, Madison, WI 53705, USA. Tel.: +1 608 262 2893; Fax: +1 608 262 5345; E-mail: jajohnson@pharmacy.wisc.edu

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Abstract

The expression of phase-II detoxification and antioxidant enzymes is governed by a cis-acting regulatory element named the antioxidant response element (ARE). ARE-containing genes are regulated by the nuclear factor erythroid-2-related factor 2 (Nrf2), a member of the Cap'n'Collar basic-leucine-zipper family of transcription factors. ARE-regulated genes are preferentially activated in astrocytes, which consequently have more efficient detoxification and antioxidant defences than neurons. Astrocytes closely interact with neurons to provide structural, metabolic and trophic support, as well as actively participating in the modulation of neuronal excitability and neurotransmission. Therefore, functional alterations in astrocytes can shape the interaction with surrounding cells, such as neurons and microglia. Activation of Nrf2 in astrocytes protects neurons from a wide array of insults in different in vitro and in vivo paradigms, confirming the role of astrocytes in determining the vulnerability of neurons to noxious stimuli. Here, we review the current data supporting Nrf2 activation in astrocytes as a viable therapeutic approach, not only in acute neuronal damage, but also in chronic neurodegeneration related to oxidative stress.

Type: Review Article
Information: Expert Reviews in Molecular Medicine , Volume 11 , July 2009 , e17

DOI: https://doi.org/10.1017/S1462399409001094 [Opens in a new window]
Copyright: Copyright © Cambridge University Press 2009

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The Nrf2–ARE cytoprotective pathway in astrocytes

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The Nrf2–ARE cytoprotective pathway in astrocytes

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