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Versatile Orphan Nuclear Receptor NR4A2 as a Promising Molecular Target for Multiple Sclerosis and Other Autoimmune Diseases

  • Shinji Oki
  • Benjamin J. E. Raveney
  • Yoshimitsu Doi
  • Takashi Yamamura
Conference paper

Abstract

The nuclear receptor family is a large group of ligand-dependent or ligand-independent transcription factors with 48 genes identified in the human genome. There is accumulating evidence that nuclear receptors are very fascinating components in terms of biological relevance to human diseases such as cancer, heart diseases, diabetes, and other lifestyle-related diseases or regulatory functions by natural and synthetic ligands. However, because of the multifunctional properties of individual nuclear receptor, the precise molecular behavior of nuclear receptors under physiological circumstances is still far from being completely understood. In addition, nuclear receptors have long been attractive drug targets and provide an enormous body of knowledge about the medicinal chemistry of their small molecule modulators. Importantly, many of the nuclear receptors are druggable targets, which is why numerous natural and synthetic nuclear receptor ligands, mostly composed of the steroid structural class, are on the market. The huge economic impact of those ligands is represented by their estimated share of 10–15% of the global pharmaceutical market. Many nuclear receptors are known as intrinsic components of immune responses including glucocorticoid receptor (GR), retinoic acid receptors (RARs), vitamin D receptor (VDR), peroxisome proliferator-activated receptors (PPARs), and retinoid orphan receptors (RORs). Herein, we discuss our recent findings that orphan nuclear receptor NR4A2 is profoundly involved in the development of autoreactive T cells and to be added to the list of beneficial molecular targets for autoimmune diseases such as multiple sclerosis.

Keywords

Multiple Sclerosis Experimental Autoimmune Encephalomyelitis Multiple Sclerosis Patient Nuclear Receptor Myelin Oligodendrocyte Glycoprotein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

AF2

Activation-function 2

CNS

Central nervous system

DBD

DNA-binding domain

EAE

Experimental autoimmune encephalomyelitis

IFN

Interferon

IL

Interleukin

LBD

Ligand-binding domain

MBP

Myelin basic protein

MHC

Major histocompatibility complex

MOG

Myelin oligodendrocyte glycoprotein

MS

Multiple sclerosis

NBRE

NGFI-B response element

NurRE

Nur-responsive element

PLP

Proteolipid protein

RXR

Retinoid X receptor

siRNA

Small interfering RNA

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Copyright information

© Springer 2012

Authors and Affiliations

  • Shinji Oki
    • 1
  • Benjamin J. E. Raveney
    • 1
  • Yoshimitsu Doi
    • 1
  • Takashi Yamamura
    • 1
  1. 1.Department of Immunology, National Institute of NeuroscienceNational Center of Neurology and PsychiatryKodaira, TokyoJapan

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