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Review
. 2013 Dec 2:6:44.
doi: 10.3389/fnmol.2013.00044.

Nur transcription factors in stress and addiction

Danae Campos-Melo  1 , Danny Galleguillos  1 , Natalia Sánchez  1 , Katia Gysling  1 , María E Andrés  1
Affiliations
Review

Nur transcription factors in stress and addiction

Danae Campos-Melo et al. Front Mol Neurosci. .

Abstract

The Nur transcription factors Nur77 (NGFI-B, NR4A1), Nurr1 (NR4A2), and Nor-1 (NR4A3) are a sub-family of orphan members of the nuclear receptor superfamily. These transcription factors are products of immediate early genes, whose expression is rapidly and transiently induced in the central nervous system by several types of stimuli. Nur factors are present throughout the hypothalamus-pituitary-adrenal (HPA) axis where are prominently induced in response to stress. Drugs of abuse and stress also induce the expression of Nur factors in nuclei of the motivation/reward circuit of the brain, indicating their participation in the process of drug addiction and in non-hypothalamic responses to stress. Repeated use of addictive drugs and chronic stress induce long-lasting dysregulation of the brain motivation/reward circuit due to reprogramming of gene expression and enduring alterations in neuronal function. Here, we review the data supporting that Nur transcription factors are key players in the molecular basis of the dysregulation of neuronal circuits involved in chronic stress and addiction.

Keywords: Nor1; Nur77; Nurr1; addiction; corticotropin releasing factor; gene expression regulation; nuclear receptors; stress.

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Figures

Figure 1
Figure 1
Scheme of Nur factors structure and DNA-binding elements. (A) Nur factors common structure, AF: activation function domain; DBD: DNA Binding Domain; LBD: Ligand Binding Domain. (B) Nur factors DNA binding elements. RXR: retinoic-X-receptor; 9-cis RA: 9-cis retinoic acid.
Figure 2
Figure 2
Nur factors are post-translational modified. (A) Phosphorylation, (B) SUMOylation, and (C) Acetylation and ubiquitination.
Figure 3
Figure 3
Expression of Nur factors in the in the motivation/reward circuit. Nurr1 is expressed in dopamine neurons of the SN/VTA and Nur77 and Nor-1 are expressed in dopamine-receptive GABAergic neurons of the striatum/NAc. GABAergic projecting neurons in the striatum/NAc are segregated in two populations that express either D1 or D2 receptors (Valjent et al., 2009).
Figure 4
Figure 4
Scheme of Nur factors expression in the HPA axis.
See this image and copyright information in PMC

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