Nur transcription factors in stress and addiction

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.

Direct conversion from skin fibroblasts to functional dopaminergic neurons for biomedical application

“…NGFI-B response element (NBRE, AAAGGTCA) is crucial for Nurr1 function as a monomer, Nurr response element (NurRE, AAAT(G/A)(C/T)CA) is important for homodimers or heterodimers with NR4A family (Nur77 or Nor1), and direct repeat of AGGTCA with a five-base-pair spacer (DR5) is required for heterodimer with RXR (Campos-Melo et al 2013). Importantly, Nurr1 induces the expression of TH as well as dopamine transporter (DAT) to maintain dopamine levels in synaptic cleft (Sakurada et al 1999;Schimmel et al 1999;Sacchetti et al 2001).…”

60 YEARS OF POMC: Transcriptional and epigenetic regulation of POMC gene expression

“…The POMC gene NurRE exhibits a preference for Nur factor dimers that include NGFI-B compared with the activity of a consensus NurRE that is equally activated by the three members of this NR subfamily (Maira et al 1999). The Nur subfamily of orphan NRs includes in addition to NGFI-B (Nur77), the factors Nur-related factor 1 (Nurr1) and NOR1 (Campos-Melo et al 2013).…”

Nuclear receptors in nematode development: Natural experiments made by a phylum

“…In vertebrates, heterodimerization partners include members of the NR1 subfamily [NR1C1-3 (PPARα,β/δ,γ), NR1B1-3 (RARα,β,γ), NRH1-2 (LXRα,β), NR1A1-2 (TRα,β), NR1I1-2 (VDR and PXR), NR1H4 (FXR)] and NR4 subfamily [NR4A1-2 (Nur77 and Nurr1)] ( [75,76]). Specific functions of RXR homodimers are also found in vertebrates and were shown to have both transactivating [77,78] as well as transrepressing regulatory functions [79].…”

“…NHR-6 NHR-6 shows close relation to NR4 subfamily members NUR77/ NGFIB (NR4A1), Nurr1 (NR4A2) and NOR-1 (NR4A3) in vertebrates and HR38 in insects (DHR38 in Drosophila). Vertebrate members are expressed in a wide range of tissues and have pleiotropic functions ranging form regulation of development and homeostasis of dopaminergic neurons, immediate stress response, cellular proliferation, apoptosis to regulation of glucose metabolism, inflammation and cancer (reviewed in [75,76,177,178]). NR4 proteins can bind response elements as monomers, homodimers and NUR77 and Nurr1 also as heterodimers with RXR [179].…”