A Nurr1/CoREST Pathway in Microglia and Astrocytes Protects Dopaminergic Neurons from Inflammation-Induced Death

Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG, Gage FH, Glass CK (2009)

Publication Type: Journal article

Publication year: 2009

Journal

Cell Elsevier

Book Volume: 137

Pages Range: 47-59

Journal Issue: 1

DOI: 10.1016/j.cell.2009.01.038

Abstract

Nurr1, an orphan nuclear receptor, plays an essential role in the generation and maintenance of dopaminergic neurons in the brain. Rare mutations in Nurr1 are associated with familial Parkinson's disease, but the underlying basis for this relationship has not been established. Here, we demonstrate that Nurr1 unexpectedly functions to inhibit expression of pro-inflammatory neurotoxic mediators in both microglia and astrocytes. Reduced Nurr1 expression results in exaggerated inflammatory responses in microglia that are further amplified by astrocytes, leading to the production of factors that cause death of tyrosine hydroxylase-expressing neurons. Nurr1 exerts anti-inflammatory effects by docking to NF-κB-p65 on target inflammatory gene promoters in a signal-dependent manner. Subsequently, Nurr1 recruits the CoREST corepressor complex, resulting in clearance of NF-κB-p65 and transcriptional repression. These studies suggest that Nurr1 protects against loss of dopaminergic neurons in Parkinson's disease in part by limiting the production of neurotoxic mediators by microglia and astrocytes. © 2009 Elsevier Inc. All rights reserved.

Authors with CRIS profile

Beate Winner

Involved external institutions

UC San Diego School of Medicine US United States (USA) (US) Salk Institute for Biological Studies US United States (USA) (US) University of California, San Diego US United States (USA) (US)

How to cite

APA:

Saijo, K., Winner, B., Carson, C.T., Collier, J.G., Boyer, L., Rosenfeld, M.G.,... Glass, C.K. (2009). A Nurr1/CoREST Pathway in Microglia and Astrocytes Protects Dopaminergic Neurons from Inflammation-Induced Death. Cell, 137(1), 47-59. https://doi.org/10.1016/j.cell.2009.01.038

MLA:

Saijo, Kaoru, et al. "A Nurr1/CoREST Pathway in Microglia and Astrocytes Protects Dopaminergic Neurons from Inflammation-Induced Death." Cell 137.1 (2009): 47-59.

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