Review

Cell and Tissue Research

, Volume 318, Issue 1, pp 45-52

Nurr1, an orphan nuclear receptor with essential functions in developing dopamine cells

  • Thomas PerlmannAffiliated withThe Ludwig InstituteDepartment of Cell and Molecular Biology, Karolinska Institutet Email author 
  • , Åsa Wallén-MackenzieAffiliated withThe Ludwig Institute

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Abstract

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.

Keywords

Nurr1 NR4A2 Nuclear receptor Orphan receptor Transcription factor Dopamine cell development Parkinson’s disease