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Annular á-synuclein species from purified multiple system atrophy inclusions
Citation
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
Abstract
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: | Medical and Health Sciences |
| Research Group: | Neurosciences |
| Research Field: | Neurology and Neuromuscular Diseases |
| Objective Division: | Health |
| Objective Group: | Clinical Health (Organs, Diseases and Abnormal Conditions) |
| Objective Field: | Nervous System and Disorders |
| Author: | Quilty, MC (Miss Marian Quilty) |
| Author: | Vickers, JC (Professor James Vickers) |
| ID Code: | 32362 |
| Year Published: | 2004 |
| Web of Science® Times Cited: | 46 |
| Deposited By: | Pathology |
| Deposited On: | 2004-08-01 |
| Last Modified: | 2005-06-22 |
| Downloads: | 0 |
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