Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/44582
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: p25α relocalizes in oligodendroglia from myelin to cytoplasmic inclusions in multiple system atrophy
Other Titles: p25alpha relocalizes in oligodendroglia from myelin to cytoplasmic inclusions in multiple system atrophy
Author: Song, Y.
Lundvig, D.
Huang, Y.
Gai, W.
Blumbergs, P.
Hojrup, P.
Otzen, D.
Halliday, G.
Jensen, P.
Citation: American Journal of Pathology, 2007; 171(4):1291-1303
Publisher: Amer Soc Investigative Pathology Inc
Issue Date: 2007
ISSN: 0002-9440
1525-2191
Statement of
Responsibility: 
Yun Ju C. Song, Ditte M.S. Lundvig, Yue Huang, Wei Ping Gai, Peter C. Blumbergs, Peter Højrup, Daniel Otzen, Glenda M. Halliday and Poul H. Jensen
Abstract: p25{alpha} is an oligodendroglial protein that can induce aggregation of {alpha}-synuclein and accumulates in oligodendroglial cell bodies containing fibrillized {alpha}-synuclein in the neurodegenerative disease multiple system atrophy (MSA). We demonstrate biochemically that p25{alpha} is a constituent of myelin and a high-affinity ligand for myelin basic protein (MBP), and in situ immunohistochemistry revealed that MBP and p25{alpha} colocalize in myelin in normal human brains. Analysis of MSA cases reveals dramatic changes in p25{alpha} and MBP throughout the course of the disease. In situ immunohistochemistry revealed a cellular redistribution of p25{alpha} immunoreactivity from the myelin to the oligodendroglial cell soma, with no overall change in p25{alpha} protein concentration using immunoblotting. Concomitantly, an ~80% reduction in the concentration of full-length MBP protein was revealed by immunoblotting along with the presence of immunoreactivity for MBP degradation products in oligodendroglia. The oligodendroglial cell bodies in MSA displayed an enlargement along with the relocalization of p25{alpha}, and this was enhanced after the deposition of {alpha}-synuclein in the glial cytoplasmic inclusions. Overall, the data indicate that changes in the cellular interactions between MBP and p25{alpha} occur early in MSA and contribute to abnormalities in myelin and subsequent {alpha}-synuclein aggregation and the ensuing neuronal degeneration that characterizes this disease.
Keywords: Oligodendroglia; Myelin Sheath; Axons; Inclusion Bodies; Cytoplasm; Animals; Cattle; Swine; Humans; Multiple System Atrophy; Nerve Tissue Proteins; alpha-Synuclein; Myelin Basic Protein
Description: Published online before print September 6, 2007
Rights: Copyright © 2007 American Society for Investigative Pathology
RMID: 0020073222
DOI: 10.2353/ajpath.2007.070201
Published version: http://ajp.amjpathol.org/cgi/reprint/171/4/1291
Appears in Collections:Pathology publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.