NR4A2 / NURR1

nuclear receptor subfamily 4, group A, member 2

Nuclear receptor Nurr1, a NR4 Nerve Growth Factor-Like Receptor, has been shown to affect the maturation, migration, striatal target area innervation, and survival of differentiating mesencephalic dopaminergic (DA) neurons. It has been shown that the receptor tyrosine kinase Ret1 is regulated by Nurr1 in midbrain dopamine neurons. Nurr1 binds to target DNA as a monomer, homodimer, or heterodimer (with retinoid X receptors). Nurr1-null mice fail to generate midbrain neurons with a dopaminergic phenotype, and midbrain dopamine precursor cells degenerate during brain development. Nurr1-null mice have similar brain structure as patients with Parkinson's disease. Mutation in the Nurr1 sequence has been documented in patients with schizophrenia and manic-depression, and more recently, in Parkinson's disease (Le et al. 2002). Nurr2, an alternatively spliced and truncated protein isoform of Nurr1, has been isolated from mouse. Nurr2 has a novel cryptic exon located upstream in the Nurr1 promoter region and is generated by alternative splicing at exons 1, 2, and 6. The existence of Nurr2 mRNA has also been reported in human and rat. Recent findings indicate that Nurr1 may play a role in mediating some of the anti-proliferative effects of 6-mercaptopurine and potentially implicate Nurr1 as a molecular target for treatment of leukemias ( Ordentlich et al. 2003).

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