Perlmann Thomas, Wallén-Mackenzie Asa
The Ludwig Institute, Stockholm, Sweden.
Cell Tissue Res. 2004 Oct;318(1):45-52. doi: 10.1007/s00441-004-0974-7. Epub 2004 Sep 1.
Nurr1 is a transcription factor that is expressed in the embryonic ventral midbrain and is critical for the development of dopamine (DA) neurons. It belongs to the conserved family of nuclear receptors but lacks an identified ligand and is therefore referred to as an orphan receptor. Recent structural studies have indicated that Nurr1 belongs to a class of ligand-independent nuclear receptors that are unable to bind cognate ligands. However, Nurr1 can promote signaling via its heterodimerization partner, the retinoid X receptor (RXR). RXR ligands can promote the survival of DA neurons via a process that depends on Nurr1-RXR heterodimers. In developing DA cells, Nurr1 is required for the expression of several genes important for DA synthesis and function. However, Nurr1 is probably also important for the maintenance of adult DA neurons and plays additional less-well-elucidated roles in other regions of the central nervous system and in peripheral tissues.
Nurr1是一种转录因子,在胚胎腹侧中脑表达,对多巴胺(DA)神经元的发育至关重要。它属于核受体的保守家族,但缺乏已确定的配体,因此被称为孤儿受体。最近的结构研究表明,Nurr1属于一类不依赖配体的核受体,无法结合同源配体。然而,Nurr1可以通过其异源二聚体伙伴视黄酸X受体(RXR)促进信号传导。RXR配体可以通过依赖于Nurr1-RXR异源二聚体的过程促进DA神经元的存活。在发育中的DA细胞中,Nurr1是几种对DA合成和功能重要的基因表达所必需的。然而,Nurr1可能对成年DA神经元的维持也很重要,并且在中枢神经系统的其他区域和外周组织中发挥其他尚未充分阐明的作用。