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PMID:16243425

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Citation

Jankovic, J, Chen, S and Le, WD The role of Nurr1 in the development of dopaminergic neurons and Parkinson's disease. Prog. Neurobiol. 77:128-38

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.

Links

PubMed Online version:10.1016/j.pneurobio.2005.09.001

Keywords

Animals; Brain/metabolism; Brain/pathology; Cell Differentiation; DNA-Binding Proteins/metabolism; Dopamine/metabolism; Humans; Neurons/metabolism; Neurons/pathology; Nuclear Receptor Subfamily 4, Group A, Member 2; Parkinson Disease/metabolism; Signal Transduction; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:PITX3

involved_in

GO:0071542: dopaminergic neuron differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:LMX1B

involved_in

GO:0071542: dopaminergic neuron differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HME1

involved_in

GO:0071542: dopaminergic neuron differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HME2

involved_in

GO:0071542: dopaminergic neuron differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FGF8

involved_in

GO:0071542: dopaminergic neuron differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NR4A2

involved_in

GO:0001764: neuron migration

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

  • results_in_movement_of:(CL:0000700)

Seeded From UniProt

complete

HUMAN:NR4A2

located_in

GO:0005634: nucleus

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

  • part_of:(CL:0000540)
  • part_of:(UBERON:0002038)|part_of:(UBERON:0002691)
  • part_of:(CL:0000540)|part_of:(UBERON:0004684)
  • part_of:(CL:0000540)|part_of:(UBERON:0002264)
  • part_of:(CL:0000540)|part_of:(UBERON:0000956)
  • part_of:(CL:0000540)|part_of:(CL:0000700)

Seeded From UniProt

complete

HUMAN:NR4A2

enables

GO:0004879: nuclear receptor activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:NR4A2

enables

GO:0003677: DNA binding

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:NR4A2

enables

GO:0046965: retinoid X receptor binding

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:NR4A2

part_of

GO:0032991: protein-containing complex

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NR4A2

involved_in

GO:1904948: midbrain dopaminergic neuron differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PAX5

involved_in

GO:0071542: dopaminergic neuron differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NR4A2

involved_in

GO:0071542: dopaminergic neuron differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SHH

involved_in

GO:0071542: dopaminergic neuron differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WNT1

involved_in

GO:0071542: dopaminergic neuron differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WNT3A

involved_in

GO:0071542: dopaminergic neuron differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PAX2

involved_in

GO:0071542: dopaminergic neuron differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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