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Activation of Peroxisome Proliferator-Activated Receptor-α Increases the Expression of Nuclear Receptor Related 1 Protein (Nurr1) in Dopaminergic Neurons
- Source :
- Mol Neurobiol
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Nuclear receptor related 1 protein (Nurr1) is an important transcription factor required for differentiation and maintenance of midbrain dopaminergic (DA) neurons. Since decrease in Nurr1 function either due to diminished expression or rare mutation is associated with Parkinson’s disease (PD), upregulation of Nurr1 may be beneficial for PD. However, such mechanisms are poorly understood. This study underlines the importance of peroxisome proliferator-activated receptor (PPAR)α in controlling the transcription of Nurr1. Our mRNA analyses followed by different immunoassays clearly indicated that PPARα agonist gemfibrozil strongly upregulated the expression of Nurr1 in wild-type, but not PPARα(−/−), DA neurons. Moreover, identification of conserved PPRE in the promoter of Nurr1 gene followed by chromatin immunoprecipitation analysis, PPRE luciferase assay, and manipulation of Nurr1 gene by viral transduction of different PPARα plasmids confirmed that PPARα was indeed involved in the expression of Nurr1. Finally, oral administration of gemfibrozil increased Nurr1 expression in vivo in nigra of wild-type, but not PPARα(−/−), mice identifying PPARα as a novel regulator of Nurr1 expression and associated protection of DA neurons.
- Subjects :
- 0301 basic medicine
Neuroscience (miscellaneous)
Administration, Oral
Peroxisome proliferator-activated receptor
Nuclear receptor related-1 protein
Article
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Fenofibrate
Downregulation and upregulation
Nuclear Receptor Subfamily 4, Group A, Member 2
Animals
PPAR alpha
Promoter Regions, Genetic
Receptor
Transcription factor
Neurons
chemistry.chemical_classification
Messenger RNA
Base Sequence
biology
Dopaminergic Neurons
Dopaminergic
Up-Regulation
Cell biology
Mice, Inbred C57BL
Substantia Nigra
030104 developmental biology
Neurology
chemistry
biology.protein
Female
Gemfibrozil
Chromatin immunoprecipitation
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15591182 and 08937648
- Volume :
- 56
- Database :
- OpenAIRE
- Journal :
- Molecular Neurobiology
- Accession number :
- edsair.doi.dedup.....d007c6b513a1befc602b4bfbcad10bed