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Open Access 01-12-2011 | Research article

Glutathione Peroxidase 4 is associated with Neuromelanin in Substantia Nigra and Dystrophic Axons in Putamen of Parkinson's brain

Authors: Frederick P Bellinger, Miyoko T Bellinger, Lucia A Seale, Andrea S Takemoto, Arjun V Raman, Takanori Miki, Amy B Manning-Boğ, Marla J Berry, Lon R White, G Webster Ross

Published in: Molecular Neurodegeneration | Issue 1/2011

Abstract

Background

Parkinson's disease is a neurodegenerative disorder characterized pathologically by the loss of nigrostriatal dopamine neurons that project from the substantia nigra in the midbrain to the putamen and caudate nuclei, leading to the clinical features of bradykinesia, rigidity, and rest tremor. Oxidative stress from oxidized dopamine and related compounds may contribute to the degeneration characteristic of this disease.

Results

To investigate a possible role of the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4) in protection from oxidative stress, we investigated GPX4 expression in postmortem human brain tissue from individuals with and without Parkinson's disease. In both control and Parkinson's samples, GPX4 was found in dopaminergic nigral neurons colocalized with neuromelanin. Overall GPX4 was significantly reduced in substantia nigra in Parkinson's vs. control subjects, but was increased relative to the cell density of surviving nigral cells. In putamen, GPX4 was concentrated within dystrophic dopaminergic axons in Parkinson's subjects, although overall levels of GPX4 were not significantly different compared to control putamen.

Conclusions

This study demonstrates an up-regulation of GPX4 in neurons of substantia nigra and association of this protein with dystrophic axons in striatum of Parkinson's brain, indicating a possible neuroprotective role. Additionally, our findings suggest this enzyme may contribute to the production of neuromelanin.

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Title: Glutathione Peroxidase 4 is associated with Neuromelanin in Substantia Nigra and Dystrophic Axons in Putamen of Parkinson's brain
Authors: Frederick P Bellinger
Miyoko T Bellinger
Lucia A Seale
Andrea S Takemoto
Arjun V Raman
Takanori Miki
Amy B Manning-Boğ
Marla J Berry
Lon R White
G Webster Ross
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2011
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/1750-1326-6-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Glutathione Peroxidase 4 is associated with Neuromelanin in Substantia Nigra and Dystrophic Axons in Putamen of Parkinson's brain

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusions

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