Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic (DA) neurons in the substantial nigra pars compacta. Increasing evidence showed that Wnt/β-catenin pathway and the orphan nuclear receptor Nurr1 play crucial roles in the survival and functional maintenance of DA neurons in the midbrain and GSK-3β antagonists LiCl and SB216763 were used to activate Wnt/β-caten...

Loss-of-function DJ-1 mutations have been linked to autosomal recessive early-onset Parikinsonism. However, the putative function of DJ-1 is not completely understood. Previous studies indicate that DJ-1 overexpression results in upregulation of the tyrosine hydroxylase gene. The mechanism by which DJ-1 affects tyrosine hydroxylase expression remains elusive. In the present study, we show that ...

The transcription factor Nurr1 is essential for dopamine neuron differentiation and is important in maintaining dopamine synthesis and neurotransmission in the adult. Reduced Nurr1 function, due to the Nurr1-null heterozygous genotype (+/-), impacts dopamine neuron function in a region specific manner resulting in a decrease in dopamine synthesis in the dorsal and ventral striatum and a decreas...

Mutations in the gene encoding the orphan nuclear receptor Nurr1 are linked to a rare familial form of Parkinson's disease. By examining the function of its mouse homolog, Saijo et al. (2009) provide evidence that Nurr1 protects dopaminergic neurons by suppressing inflammatory gene expression in astrocytes and microglia.

The purine anti-metabolite 6-mercaptopurine is one of the most widely used drugs for the treatment of acute childhood leukemia and chronic myelocytic leukemia. Developed in the 1950s, the drug is also being used as a treatment for inflammatory diseases such as Crohn's disease. The antiproliferative mechanism of action of this drug and other purine anti-metabolites has been demonstrated to be th...

Here, we study the expression of NURR1 and FOXA1 mRNA in peripheral blood lymphocytes and its haplotypes in coding region in a small Chennai population of India. Thirty cases of Parkinson's patients (PD) with anti-PD medications (20 males aged 65.85 ± 1.19 and 10 females aged 65.7 ± 1.202) and 30 age matched healthy people (20 males aged 68.45 ± 1.282 and 10 females aged 65.8 ± 1.133) were incl...

Dopaminergic neurons in the substantia nigra pars compacta (SNpc) are characterized by the expression of genes required for dopamine synthesis, handling and reuptake and the expression of these genes is largely controlled by nuclear receptor related 1 (Nurr1). Nurr1 is also expressed in astrocytes and microglia where it functions to mitigate the release of proinflammatory cytokines and neurotox...

α-Synuclein (α-syn) plays a prominent role in the degeneration of midbrain dopaminergic (mDA) neurons in Parkinson's disease (PD). However, only a few studies on α-syn have been performed in the mDA neurons in vivo, which may be attributed to a lack of α-syn transgenic mice that develop PD-like severe degeneration of mDA neurons. To gain mechanistic insights into the α-syn-induced mDA neurodege...

Because the dopaminergic pathways in the midbrain have been closely associated with serious neuropsychiatric disorders, the elucidation of the mechanisms underlying dopaminergic neuronal development should provide some important clues for related disorders. In mice lacking the dopamine D2 receptor (D2R-/-), stereological cell counting analysis showed that the number of mesencephalic tyrosine hy...

In addition to its role as a 9-cis retinoic acid receptor, RXR has an important role in the regulation of multiple hormonal pathways through heterodimerization with nuclear receptors. Here, we show that two orphan receptors, NGFI-B and NURR1, which have been shown previously to interact with DNA as monomers, also can heterodimerize with RXR. These heterodimers bind selectively to a class of ret...