Nur77

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Petr75
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Nur77

Post by Petr75 »

2020 Jun 6
Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, China
Progress and Promise of Nur77-based Therapeutics for Central Nervous System Disorders
https://pubmed.ncbi.nlm.nih.gov/32504502/

Abstract

Nur77 belongs to the NR4A subgroup of the nuclear receptor superfamily. Unlike other nuclear receptors, a natural ligand for Nur77 has not been identified yet. However, a few small molecules can interact with this receptor and induce a conformational change to mediate its activity. The expression and activation of Nur77 can be rapidly increased using various physiological and pathological stimuli. In vivo and in vitro studies have demonstrated its regulatory role in tissues and cells of multiple systems by means of participation in cell differentiation, apoptosis, metabolism, mitochondrial homeostasis, and other processes. Although research on Nur77 in the pathophysiology of the central nervous system (CNS) is currently limited, the present data support the fact that Nur77 is involved in many neurological disorders such as stroke, multiple sclerosis, Parkinson's disease. This indicates that activation of Nur77 has considerable potential in treating these diseases. This review summarizes the regulatory mechanisms of Nur77 in CNS diseases and presents available evidence for its potential as a targeted therapy, especially for cerebrovascular and inflammation-related CNS diseases.
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NHE
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Re: Nur77

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Nur77 Serves as a Molecular Brake of the Metabolic Switch During T Cell Activation to Restrict Autoimmunity
Proc Natl Acad Sci U S A. 2018 Aug 21;115(34):E8017-E8026.

T cells critically depend on reprogramming of metabolic signatures to meet the bioenergetic demands during activation and clonal expansion. Here we identify the transcription factor Nur77 as a cell-intrinsic modulator of T cell activation. Nur77-deficient T cells are highly proliferative, and lack of Nur77 is associated with enhanced T cell activation and increased susceptibility for T cell-mediated inflammatory diseases, such as CNS autoimmunity, allergic contact dermatitis and collagen-induced arthritis. Importantly, Nur77 serves as key regulator of energy metabolism in T cells, restricting mitochondrial respiration and glycolysis and controlling switching between different energy pathways. Transcriptional network analysis revealed that Nur77 modulates the expression of metabolic genes, most likely in close interaction with other transcription factors, especially estrogen-related receptor α. In summary, we identify Nur77 as a transcriptional regulator of T cell metabolism, which elevates the threshold for T cell activation and confers protection in different T cell-mediated inflammatory diseases.

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