α‐Synuclein Immunoisolation of Glial Inclusions from Multiple System Atrophy Brain Tissue Reveals Multiprotein Components

Immunohistochemical studies have shown that oligodendroglial inclusions in multiple system atrophy contain alpha-synuclein, a synaptic protein also found in Lewy bodies in Parkinson's disease. We have now used density gradient enrichment and an anti-alpha-synuclein immunomagnetic technique to i...

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Bibliographic Details
Published in:Journal of neurochemistry 1999-11, Vol.73 (5), p.2093-2100
Main Authors: GAI, W. P, POWER, J. H. T, BLUMBERGS, P. C, CULVENOR, J. G, JENSEN, P. H
Format: Article
Language:English
Subjects:
a-Synuclein
Aged
alpha-Synuclein
Biological and medical sciences
Biotinylation
Brain - ultrastructure
Cell Fractionation - methods
Centrifugation, Density Gradient
Crystallins - analysis
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Female
Humans
Immunoblotting
Immunomagnetic Separation
inclusion bodies
Inclusion Bodies - chemistry
Inclusion Bodies - ultrastructure
Medical sciences
Microscopy, Electron
Middle Aged
multiple system atrophy
Multiple System Atrophy - pathology
Nerve Tissue Proteins - analysis
Nerve Tissue Proteins - immunology
Neuroglia - ultrastructure
Neurology
Synucleins
Tubulin - analysis
Ubiquitins - analysis
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Summary:Immunohistochemical studies have shown that oligodendroglial inclusions in multiple system atrophy contain alpha-synuclein, a synaptic protein also found in Lewy bodies in Parkinson's disease. We have now used density gradient enrichment and an anti-alpha-synuclein immunomagnetic technique to isolate pure and morphologically intact oligodendroglial inclusions from brain white matter of patients dying with multiple system atrophy. Filamentous inclusion structures were obtained only from multiple system atrophy tissue, but not from normal brain tissues, or from multiple system atrophy tissue processed without anti-alpha-synuclein antibody. We confirmed the purity and morphology of isolated inclusions by electron microscopy. The inclusions comprised multiple protein bands after separation by polyacrylamide gel electrophoresis. Immunoblotting demonstrated that these proteins included alpha-synuclein, alphaB-crystallin, tubulins, ubiquitin, and prominent, possibly truncated alpha-synuclein species as high-molecular-weight aggregates. Our study provides the first biochemical evidence that oligodendroglial inclusion filaments consist of multiple protein components, suggesting that these inclusions may form as a result of multiprotein interactions with alpha-synuclein.
ISSN:0022-3042
1471-4159
DOI:10.1046/j.1471-4159.1999.02093.x