The role of Nurr1 in the development of dopaminergic neurons and Parkinson's disease

J. Jankovic, S. Chen, Weidong Le

Research output: Contribution to journalReview articlepeer-review

226 Scopus citations

Abstract

Nurr1, a transcription factor belonging to the orphan nuclear receptor superfamily, is critical in the development and maintenance of the dopaminergic system and as such it may have role in the pathogenesis of Parkinson' disease (PD). Human Nurr1 gene has been mapped to chromosome 2q22-23 and Nurr1 protein is predominantly expressed in central dopaminergic neurons. Nurr1 interacts with other factors critical for the survival of mensencephalic dopaminergic neurons and it appears to regulate the expression of tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and l-aromatic amino acid decarboxylase (AADC), all of which are important in the synthesis and storage of dopamine. Experimental studies in Nurr1 knock-out mice indicate that Nurr1 deficiency results in impaired dopaminergic function and increased vulnerability of those midbrain dopaminergic neurons that degenerate in PD. Decreased Nurr1 expression is found in the autopsied PD midbrains, particularly in neurons containing Lewy bodies, as well as in peripheral lymphocytes of patients with parkinsonian disorders. Several variants in Nurr1 gene have been reported in association with PD. All these studies suggest that Nurr1 is not only essential in the development of mensencephalic dopaminergic neurons and maintenance of their functions, but it may also play a role in the pathogenesis of PD.

Original languageEnglish (US)
Pages (from-to)128-138
Number of pages11
JournalProgress in Neurobiology
Volume77
Issue number1-2
DOIs
StatePublished - 2005

Keywords

  • Dopaminergic neuron
  • Nurr1
  • Parkinson's disease
  • Polymorphisms
  • Transcriptional factor

ASJC Scopus subject areas

  • Neuroscience(all)

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