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Association of Metallothionein-III with Oligodendroglial Cytoplasmic Inclusions in Multiple System Atrophy
Citation
Pountney, DL and Dickson, TC and Power, JHT and Vickers, JC and West, AK and Gai, WP, Association of Metallothionein-III with Oligodendroglial Cytoplasmic Inclusions in Multiple System Atrophy, Neurotoxicity Research: An International Journal on Processes and Mechanisms in Neurodegeneration, Apoptosis, Neuroprotection and Regeneration, 19, (1) pp. 115-122. ISSN 1029-8428 (2011) [Refereed Article]
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Copyright Statement
Copyright © Springer Science+Business Media, LLC 2009 The final publication is available at http://www.springerlink.com
DOI: doi:10.1007/s12640-009-9146-6
Abstract
Multiple system atrophy (MSA) is an adultonset
neurodegenerative disease characterised by Parkinsonian
and autonomic symptoms and by widespread
intracytoplasmic inclusion bodies in oligodendrocytes.
These glial cytoplasmic inclusions (GCIs) are comprised of
9–10 nm filaments rich in the protein alpha-synuclein, also
found in neuronal inclusion bodies associated with Parkinson’s
disease. Metallothioneins (MTs) are a class of
low-molecular weight (6–7 kDa), cysteine-rich metalbinding
proteins the expression of which is induced by
heavy metals, glucocorticoids, cytokines and oxidative
stress. Recent studies have shown a role for the ubiquitously
expressed MT-I/II isoforms in the brain following a
variety of stresses, whereas, the function of the brain-specific
MT isoform, MT-III, is less clear. MT-III and MT-I/II
immunostaining of post-mortem tissue in MSA and normal
control human brains showed that the number of MT-IIIpositive
cells is significantly increased in MSA in visual
cortex, whereas MT-I/II isoforms showed no significant
difference in the distribution of immunopositive cells in
MSA compared to normal tissue. GCIs were immunopositive
for MT-III, but were immunonegative for the MT-I/II
isoforms. Immunofluorescence double labelling showed the
co-localisation of alpha-synuclein and MT-III in GCIs
in MSA tissue. In isolated GCIs, transmission electron
microscopy demonstrated MT-III immunogold labelling of
the amorphous material surrounding alpha-synuclein filaments
in GCIs. High-molecular weight MT-III species in
addition to MT-III monomer were detected in GCIs by
Western analysis of the detergent-solubilised proteins of
purified GCIs. These results show that MT-III, but not MTI/
II, is a specific component of GCIs, present in abnormal
aggregated forms external to the alpha-synuclein filaments.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | Metallothionein, Multiple system atrophy, Inclusion body, á-Synuclein |
| Research Division: | Medical and Health Sciences |
| Research Group: | Neurosciences |
| Research Field: | Cellular Nervous System |
| Objective Division: | Health |
| Objective Group: | Clinical Health (Organs, Diseases and Abnormal Conditions) |
| Objective Field: | Nervous System and Disorders |
| Author: | Dickson, TC (Professor Tracey Dickson) |
| Author: | Vickers, JC (Professor James Vickers) |
| Author: | West, AK (Professor Adrian West) |
| ID Code: | 72160 |
| Year Published: | 2011 |
| Web of Science® Times Cited: | 9 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2011-08-23 |
| Last Modified: | 2017-11-06 |
| Downloads: | 0 |
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