Cited by 326Nuclear Receptors and SignalingParkinson's Disease Mechanisms and TreatmentsNeurotransmitter Receptor Influence on Behavior

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

Jankovic, J., Chen, S., Le, W.D.·2005·Progress in Neurobiology

DOI 10.1016/j.pneurobio.2005.09.001

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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.

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Jiang, 2004, Effects of ropinirole on progression of parkinsonism in Nurr1 deficient mice and its underlying mechanism, Neurology, 62, A7
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Pan, 2005, Reduction of Nurr1 mRNA in human peripheral blood lymphocytes in Parkinson disease, Ann. Neurol.
Pan, 2005, Radicicol induces heat shock protein expression and neuroprotection against rotenone-mediated apoptosis in SH-SY5Y cells, Mov. Dis., S86

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See all 326

Authors: Jankovic, J., Chen, S., & Le, W. D.
Affiliations: Baylor College of Medicine (US)
Shanghai Jiao Tong University (CN)
Corresponding author: Le, W.D.
ORCID: Jankovic, J.
Chen, S.
Le, W.D.
Venue: Progress in Neurobiology
Publisher: Elsevier BV
Published: 2005-09
Volume: 77
Issue: 1-2
Pages: 128-138
ISSN: 0301-0082 (ISSN-L)
DOI: 10.1016/j.pneurobio.2005.09.001
OpenAlex: W2048841722
Cited by: 325
References: 89
Citations by year: 2026: 10 · 2025: 8 · 2024: 15 · 2023: 14 · 2022: 21 · 2021: 22 · 2020: 13 · 2019: 19 · 2018: 13 · 2017: 19 · 2016: 15 · 2015: 18 · 2014: 16 · 2013: 22 · 2012: 16
FWCI: 1.06
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Progress in Neurobiology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute of Neurological Disorders and Stroke (NS043567, R01NS043567, NS40370, R01NS040370)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: Nurr1, Parkinson's disease, dopaminergic neurons, midbrain, transcription factors, orphan nuclear receptor, tyrosine hydroxylase, dopamine transporter, vesicular monoamine transporter 2, aromatic L-amino acid decarboxylase, Lewy bodies, dopaminergic neuron development, dopaminergic neuron survival
MeSH terms: Animals, Brain, Cell Differentiation, DNA-Binding Proteins, Dopamine, Humans, Neurons, Parkinson Disease, Transcription Factors, Signal Transduction, Nuclear Receptor Subfamily 4, Group A, Member 2

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

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