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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-4-24
pubmed:abstractText
Multiple system atrophy (MSA) belongs to synucleinopathies and is characterized pathologically by oligodendroglial inclusions (GCIs) composed of 20- to 30-nm tubular filaments. alpha-Synuclein fibrils formed in vitro, however, range between 10 and 12 nm in diameter. To understand the relationship between alpha-synuclein and GCI filaments, we conducted structural analyses of GCIs in fixed brain sections and isolated from fresh-frozen MSA brains. In fixed brain sections, GCIs were composed of amorphous material-coated filaments up to 30 nm in size. The filaments were often organized in parallel bundles extending into oligodendroglial processes. In freshly isolated GCIs, progressive buffer washes removed amorphous material and revealed that GCI filaments consisted of 10-nm-sized central core fibrils that were strongly alpha-synuclein immunoreactive. Image analysis revealed that each core fibril was made of two subfibrils, and each subfibril was made of a string of 3- to 6-nm-sized particles probably alpha-synuclein oligomers. Immunogold labeling demonstrated that epitopes encompassing entire alpha-synuclein molecule were represented in the core fibrils, with the N-terminal 11-26 and C-terminal 108-131 amino acid residues most accessible to antibodies, probably exposed on the surface of the fibril. Our study indicates that GCI filaments are multilayered in structure, with alpha-synuclein oligomers forming the central core fibrils of the filaments.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0014-4886
pubmed:author
pubmed:issnType
Print
pubmed:volume
181
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
68-78
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
alpha-Synuclein fibrils constitute the central core of oligodendroglial inclusion filaments in multiple system atrophy.
pubmed:affiliation
Department of Physiology and Centre for Neuroscience, Flinders University, Bedford Park, SA 5042, Australia. weiping.gai@flinders.edu.au
pubmed:publicationType
Journal Article