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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 Type:	Refereed Article
Keywords:	Metallothionein, Multiple system atrophy, Inclusion body, á-Synuclein
Research Division:	Biomedical and Clinical Sciences
Research Group:	Neurosciences
Research Field:	Cellular nervous system
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Dickson, TC (Professor Tracey Dickson)
UTAS Author:	Vickers, JC (Professor James Vickers)
UTAS Author:	West, AK (Professor Adrian West)
ID Code:	72160
Year Published:	2011
Web of Science® Times Cited:	16
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2011-08-23
Last Modified:	2017-11-06
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