Annular á-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]
Oligodendroglial cytoplasmic inclusions composed of Î±-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 Î±-synuclein species. To analyse these species, we immunopurified Î±-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-Î±-synuclein antibody confirmed that the annular structures were positive for Î±-synuclein. In contrast to pathological Î±-synuclein, detergent treatment of recombinant Î±-synuclein yielded only smaller, 10-18 nm spherical particles. Our results demonstrate that detergent treatment of pathological MSA Î±-synuclein aggregates, but not recombinant Î±-synuclein, yields discrete Î±-synuclein-positive species with annular morphologies. The ability of the pathological Î±-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 Î±-synuclein aggregates.