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Annular á-synuclein species from purified multiple system atrophy inclusions

journal contribution
posted on 2023-05-16, 16:00 authored by Pountney, DL, Lowe, R, Quilty, MC, James VickersJames Vickers, Voelcker, NH, Gai, WP
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.

History

Publication title

Journal of Neurochemistry

Volume

90

Pagination

502-512

ISSN

0022-3042

Department/School

Tasmanian School of Medicine

Publisher

Blackwell Publishing

Place of publication

Oxford, England

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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