Format

Send to

Choose Destination
Neuropathology. 2015 Dec;35(6):503-9. doi: 10.1111/neup.12210. Epub 2015 Jun 12.

Localization of nuclear receptor subfamily 4, group A, member 3 (NR4A3) in Lewy body disease and multiple system atrophy.

Author information

1
Department of Neuropathology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
2
Department of Neurology, Aomori Prefectural Central Hospital, Aomori, Japan.
3
Department of Pathology, Center for Bioresource-based Researches, Brain Research Institute, University of Niigata, Niigata, Japan.
4
Department of Pathological Neuroscience, Center for Bioresource-based Researches, Brain Research Institute, University of Niigata, Niigata, Japan.
5
Department of Neurology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Abstract

Nuclear receptor subfamily 4, group A, member 3 (NR4A3), also known as neuron-derived orphan receptor-1, is a nuclear receptor which plays key roles in cell cycle, neuronal differentiation, apoptosis and metabolism. These processes may be involved in the pathogenesis of certain neurodegenerative diseases. Previous studies have shown that there are high levels of NR4A3 mRNA in the CNS. Moreover, NR4A2, a transcription factor with homology to NR4A3, has been reported to contribute to the pathogenesis of Parkinson's disease. However, it is uncertain whether NR4A3 is also involved in diseases such as dementia with Lewy bodies, multiple system atrophy, and other neurodegenerative disorders such as tauopathies, TDP-43 proteinopathies and polyglutamine diseases. In the present study we used immunohistochemistry to examine the brain and spinal cord from patients with various neurodegenerative diseases and normal control subjects using two polyclonal anti-NR4A3 antibodies. In controls, the cytoplasm of neurons and glial cells was faintly immunostained with anti-NR4A3 antibodies. In tissues from patients with neurodegenerative diseases, immunoreactivity for NR4A3 was observed in cortical and brainstem-type Lewy bodies in Parkinson's disease and in dementia with Lewy bodies, as well as in neuronal and glial cytoplasmic inclusions in multiple system atrophy. A double-labeled immunofluorescence study showed co-localization of NR4A3 and phosphorylated α-synuclein in these inclusions. Neuronal and glial inclusions in other neurodegenerative disorders were NR4A3 negative. These findings suggest that accumulation of NR4A3 is specific to α-synucleinopathy.

KEYWORDS:

Lewy body; NR4A3; Parkinson's disease; multiple system atrophy; α-synuclein

PMID:
26096603
DOI:
10.1111/neup.12210
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center