Skip to main content
Journal cover image

Nrf2-mediated protection against 6-hydroxydopamine.

Publication ,  Journal Article
Jakel, RJ; Townsend, JA; Kraft, AD; Johnson, JA
Published in: Brain Res
May 4, 2007

Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by cell loss in the substantia nigra resulting in striatal dopamine depletion. Although the cause of sporadic PD is unknown, oxidative stress is thought to contribute to disease pathogenesis. One mechanism by which cells defend themselves against oxidative stress is through the transcriptional upregulation of cytoprotective genes. Under oxidative stress conditions, the transcription factor NF-E2-related factor (Nrf2) binds to the antioxidant response element (ARE) to induce antioxidant and phase II detoxification enzymes. Here we show that loss of Nrf2-mediated transcription exacerbates vulnerability to the neurotoxin 6-hydroxydopamine (6-OHDA) both in vitro and in vivo. We further demonstrate that activation of the Nrf2-ARE pathway by the known chemical inducer tert-butylhydroquinone can protect against 6-OHDA in vitro. Induction of this pathway by transplantation of astrocytes overexpressing Nrf2 can protect against 6-OHDA-induced damage in the living mouse. This suggests that the Nrf2-ARE pathway is a promising target for therapeutics aimed at reducing or preventing cell death in PD.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Brain Res

DOI

ISSN

0006-8993

Publication Date

May 4, 2007

Volume

1144

Start / End Page

192 / 201

Location

Netherlands

Related Subject Headings

  • Tyrosine 3-Monooxygenase
  • Transfection
  • Oxidopamine
  • Neurotoxins
  • Neurons
  • Neurology & Neurosurgery
  • NF-E2 Transcription Factor, p45 Subunit
  • Mice, Knockout
  • Mice
  • In Situ Nick-End Labeling
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Jakel, R. J., Townsend, J. A., Kraft, A. D., & Johnson, J. A. (2007). Nrf2-mediated protection against 6-hydroxydopamine. Brain Res, 1144, 192–201. https://doi.org/10.1016/j.brainres.2007.01.131
Jakel, Rebekah J., Jessica A. Townsend, Andrew D. Kraft, and Jeffrey A. Johnson. “Nrf2-mediated protection against 6-hydroxydopamine.Brain Res 1144 (May 4, 2007): 192–201. https://doi.org/10.1016/j.brainres.2007.01.131.
Jakel RJ, Townsend JA, Kraft AD, Johnson JA. Nrf2-mediated protection against 6-hydroxydopamine. Brain Res. 2007 May 4;1144:192–201.
Jakel, Rebekah J., et al. “Nrf2-mediated protection against 6-hydroxydopamine.Brain Res, vol. 1144, May 2007, pp. 192–201. Pubmed, doi:10.1016/j.brainres.2007.01.131.
Jakel RJ, Townsend JA, Kraft AD, Johnson JA. Nrf2-mediated protection against 6-hydroxydopamine. Brain Res. 2007 May 4;1144:192–201.
Journal cover image

Published In

Brain Res

DOI

ISSN

0006-8993

Publication Date

May 4, 2007

Volume

1144

Start / End Page

192 / 201

Location

Netherlands

Related Subject Headings

  • Tyrosine 3-Monooxygenase
  • Transfection
  • Oxidopamine
  • Neurotoxins
  • Neurons
  • Neurology & Neurosurgery
  • NF-E2 Transcription Factor, p45 Subunit
  • Mice, Knockout
  • Mice
  • In Situ Nick-End Labeling