The Role of Citrullinated Proteins Suggests a Novel Mechanism in the Pathogenesis of Multiple Sclerosis

The Role of Citrullinated Proteins Suggests a Novel Mechanism in the Pathogenesis of Multiple Sclerosis

The pathogenesis of MS is unknown. In our studies, we have demonstrated an important role for citrullinated myelin basic protein (MBP). The accompanying loss of positive charge compromises the ability of MBP to interact with the lipid bilayer. The conversion of arginine to citrulline in brain is car...

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Main Authors: Moscarello, Mario A., Mastronardi, Fabrizio G., Wood, D. Denise
Format: Online
Language:English
Published: Kluwer Academic Publishers-Plenum Publishers 2006
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1794624/
id pubmed-1794624
recordtype oai_dc
spelling pubmed-17946242007-02-08 The Role of Citrullinated Proteins Suggests a Novel Mechanism in the Pathogenesis of Multiple Sclerosis Moscarello, Mario A. Mastronardi, Fabrizio G. Wood, D. Denise Original Paper The pathogenesis of MS is unknown. In our studies, we have demonstrated an important role for citrullinated myelin basic protein (MBP). The accompanying loss of positive charge compromises the ability of MBP to interact with the lipid bilayer. The conversion of arginine to citrulline in brain is carried out by an enzyme peptidyl arginine deiminase (PAD) 2. The amount of PAD 2 in brain was increased in MS normal-appearing white matter. The mechanism responsible for this increase involved hypomethylation of the promoter region in the PAD 2 gene in MS, but no change (compared to normal) was found in thymus tissue DNA from the same MS patients. In addition, no change was observed in other neurological diseases, including Alzheimer’s, Parkinson’s, and Huntington’s. We propose that citrullinated MBP, resulting from elevated levels of PAD 2 represents an important biochemical pathway in the pathogenesis of MS. Kluwer Academic Publishers-Plenum Publishers 2006-09-22 2007-02 /pmc/articles/PMC1794624/ /pubmed/17031564 http://dx.doi.org/10.1007/s11064-006-9144-5 Text en © Springer Science+Business Media, LLC 2006
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Moscarello, Mario A.
Mastronardi, Fabrizio G.
Wood, D. Denise
spellingShingle Moscarello, Mario A.
Mastronardi, Fabrizio G.
Wood, D. Denise
The Role of Citrullinated Proteins Suggests a Novel Mechanism in the Pathogenesis of Multiple Sclerosis
author_facet Moscarello, Mario A.
Mastronardi, Fabrizio G.
Wood, D. Denise
author_sort Moscarello, Mario A.
title The Role of Citrullinated Proteins Suggests a Novel Mechanism in the Pathogenesis of Multiple Sclerosis
title_short The Role of Citrullinated Proteins Suggests a Novel Mechanism in the Pathogenesis of Multiple Sclerosis
title_full The Role of Citrullinated Proteins Suggests a Novel Mechanism in the Pathogenesis of Multiple Sclerosis
title_fullStr The Role of Citrullinated Proteins Suggests a Novel Mechanism in the Pathogenesis of Multiple Sclerosis
title_full_unstemmed The Role of Citrullinated Proteins Suggests a Novel Mechanism in the Pathogenesis of Multiple Sclerosis
title_sort role of citrullinated proteins suggests a novel mechanism in the pathogenesis of multiple sclerosis
description The pathogenesis of MS is unknown. In our studies, we have demonstrated an important role for citrullinated myelin basic protein (MBP). The accompanying loss of positive charge compromises the ability of MBP to interact with the lipid bilayer. The conversion of arginine to citrulline in brain is carried out by an enzyme peptidyl arginine deiminase (PAD) 2. The amount of PAD 2 in brain was increased in MS normal-appearing white matter. The mechanism responsible for this increase involved hypomethylation of the promoter region in the PAD 2 gene in MS, but no change (compared to normal) was found in thymus tissue DNA from the same MS patients. In addition, no change was observed in other neurological diseases, including Alzheimer’s, Parkinson’s, and Huntington’s. We propose that citrullinated MBP, resulting from elevated levels of PAD 2 represents an important biochemical pathway in the pathogenesis of MS.
publisher Kluwer Academic Publishers-Plenum Publishers
publishDate 2006
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1794624/
_version_ 1611394116319444992

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