The first two authors contributed equally to this work.
Nurr1 in Parkinson's disease and related disorders
Article first published online: 30 NOV 2005
Copyright © 2005 Wiley-Liss, Inc.
Journal of Comparative Neurology
Volume 494, Issue 3, pages 495–514, 20 January 2006
How to Cite
Chu, Y., Le, W., Kompoliti, K., Jankovic, J., Mufson, E. J. and Kordower, J. H. (2006), Nurr1 in Parkinson's disease and related disorders. J. Comp. Neurol., 494: 495–514. doi: 10.1002/cne.20828
- Issue published online: 30 NOV 2005
- Article first published online: 30 NOV 2005
- Manuscript Accepted: 22 AUG 2005
- Manuscript Revised: 6 JUN 2005
- Manuscript Received: 15 APR 2005
- Parkinson's Disease Foundation
- Rush Neurological Sciences
- National Institute of Neurological Disorders and Stroke. Grant Numbers: NS40370, NSNS043567
- National Institute on Aging. Grant Numbers: AG14449, AG10161
- transcription factor;
- dopaminergic neuron;
- substantia nigra
In mammals, the transcription factor Nurr1 is expressed early in development and continues to be detectable throughout the organism's lifetime. Nurr1 is involved in the establishment and maintenance of the dopaminergic phenotype within specific central nervous system neuronal subpopulations including the nigrostriatal dopamine system. This protein is reduced over the course of normal aging, which is a major risk factor for Parkinson's disease (PD). However, whether Nurr1 expression is affected by PD has not been documented. The present study examined the role of Nurr1 in the maintenance of the dopaminergic phenotype within neurons in substantia nigra in PD compared with patients with diagnoses of progressive supranuclear palsy (PSP) or Alzheimer's disease (AD) or age-matched-matched controls. In PD, the optical density (OD) of Nurr1 immunofluorescence was significantly decreased in nigral neurons containing α-synuclein-immunoreactive inclusions. Similarly, the OD of Nurr1 immunofluorescence intensity in the nigra of AD cases was decreased in neurons with neurofibrillary tangles (NFTs). In contrast to PD and AD, the OD of Nurr1 immunofluorescence intensity was severely decreased in the neurons with or without NFTs in PSP cases. Decline of Nurr1-ir neuronal number and OD was observed within substantia nigra (SN) neurons in PD but not within hippocampal neurons. The decline in Nurr1-ir expression was correlated with loss of tyrosine hydroxylase immunofluorescence across the four groups. These data demonstrate that Nurr1 deficiency in dopaminergic neurons is associated with the intracellular pathology in both synucleinopathies and tauopathies. J. Comp. Neurol. 494:495–514, 2006. © 2005 Wiley-Liss, Inc.