dc.contributor.author | Pountney, DL | |
dc.contributor.author | Lowe, R | |
dc.contributor.author | Quilty, M | |
dc.contributor.author | Vickers, JC | |
dc.contributor.author | Voelcker, NH | |
dc.contributor.author | Gai, WP | |
dc.date.accessioned | 2017-05-03T15:03:35Z | |
dc.date.available | 2017-05-03T15:03:35Z | |
dc.date.issued | 2004 | |
dc.identifier.issn | 0022-3042 | |
dc.identifier.doi | 10.1111/j.1471-4159.2004.02533.x | |
dc.identifier.uri | http://hdl.handle.net/10072/16891 | |
dc.description.abstract | Oligodendroglial cytoplasmic inclusions composed of a-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 a-synuclein species. To analyse these species, we immunopurified a-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) dimethyl-ammonio]-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-a-synuclein antibody confirmed that the annular structures were positive for a-synuclein. In contrast to pathological a-synuclein, detergent treatment of recombinant a-synuclein yielded only smaller, 10-18 nm spherical particles. Our results demonstrate that detergent treatment of pathological MSA a-synuclein aggregates, but not recombinant a-synuclein, yields discrete a-synuclein-positive species with annular morphologies. The ability of the pathological a-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 a-synuclein aggregates. | |
dc.description.peerreviewed | Yes | |
dc.description.publicationstatus | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Blackwell | |
dc.publisher.place | Oxford | |
dc.relation.ispartofpagefrom | 502 | |
dc.relation.ispartofpageto | 512 | |
dc.relation.ispartofissue | 2 | |
dc.relation.ispartofjournal | Journal of Neurochemistry | |
dc.relation.ispartofvolume | 90 | |
dc.subject.fieldofresearch | Biochemistry and cell biology | |
dc.subject.fieldofresearch | Neurosciences | |
dc.subject.fieldofresearchcode | 3101 | |
dc.subject.fieldofresearchcode | 3209 | |
dc.title | Annular α-synuclein species from purified multiple system atrophy inclusions | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
gro.date.issued | 2015-05-12T05:11:30Z | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Pountney, Dean L. | |