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Annular -synuclein species from purified multiple system atrophy inclusions


Pountney, DL and Lowe, R and Quilty, MC and Vickers, JC and Voelcker, NH and Gai, WP, Annular a-synuclein species from purified multiple system atrophy inclusions, Journal of Neurochemistry, 90, (2) pp. 502-512. ISSN 0022-3042 (2004) [Refereed Article]

DOI: doi:10.1111/j.1471-4159.2004.02533.x


Oligodendroglial cytoplasmic inclusions composed of α-synuclein filamentous aggregates are the pathological hallmark of multiple system atrophy (MSA). We found that cortical tissue from MSA cases contains increased detergent-resistant high-molecular-weight α-synuclein species. To analyse these species, we immunopurified α-synuclein aggregates from pathological samples and examined their ultrastructures using scanning electron and atomic force microscopies. Purified aggregates consisted of bundles of filaments. After treatment with 1% sarcosine or 2% 3-[(3-cholamidopropyl) dimethylammonio]-1- propanesulfonate (CHAPS) detergents, we observed frequent 30-50 nm annular particles, probably released from pathological aggregates due to the dissociation of filaments by the detergents. Antibody recognition imaging using a specific anti-α-synuclein antibody confirmed that the annular structures were positive for α-synuclein. In contrast to pathological α-synuclein, detergent treatment of recombinant α-synuclein yielded only smaller, 10-18 nm spherical particles. Our results demonstrate that detergent treatment of pathological MSA α-synuclein aggregates, but not recombinant α-synuclein, yields discrete α-synuclein-positive species with annular morphologies. The ability of the pathological α-synuclein to form annular aggregates may be an important factor contributing to the toxicity of the protein in disease that may have implications in designing therapeutic strategies aimed at detoxifying α-synuclein aggregates.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurology and neuromuscular diseases
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Quilty, MC (Miss Marian Quilty)
UTAS Author:Vickers, JC (Professor James Vickers)
ID Code:32362
Year Published:2004
Web of Science® Times Cited:54
Deposited By:Pathology
Deposited On:2004-08-01
Last Modified:2005-06-22

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