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Annular α‐synuclein species from purified multiple system atrophy inclusions
Author(s) -
Pountney Dean L.,
Lowe Rachel,
Quilty Marian,
Vickers James C.,
Voelcker Nicolas H.,
Gai Wei Ping
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02533.x
Subject(s) - sarcosine , cytoplasmic inclusion , chemistry , pathological , biophysics , atrophy , dissociation (chemistry) , pathology , cytoplasm , recombinant dna , alpha synuclein , protein aggregation , inclusion bodies , synuclein , biology , biochemistry , disease , parkinson's disease , medicine , amino acid , glycine , gene
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) 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‐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.