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Myelin Basic Protein Citrullination in Multiple Sclerosis: A Potential Therapeutic Target for the Pathology

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Abstract

Multiple sclerosis (MS) is a multifactorial demyelinating disease characterized by neurodegenerative events and autoimmune response against myelin component. Citrullination or deimination, a post-translational modification of protein-bound arginine into citrulline, catalyzed by Ca2+ dependent peptidylarginine deiminase enzyme (PAD), plays an essential role in physiological processes include gene expression regulation, apoptosis and the plasticity of the central nervous system, while aberrant citrullination can generate new epitopes, thus involving in the initiation and/or progression of autoimmune disorder like MS. Myelin basic protein (MBP) is the major myelin protein and is generally considered to maintain the stability of the myelin sheath. This review describes the MBP citrullination and its consequence, as well as offering further support for the “inside-out” hypothesis that MS is primarily a neurodegenerative disease with secondary inflammatory demyelination. In addition, it discusses the role of MBP citrullination in the immune inflammation and explores the potential of inhibition of PAD enzymes as a therapeutic strategy for the disease.

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Abbreviations

Anti-CCP:

Anticyclic citrullinated peptide

BBB:

Blood–brain barrier

CNS:

Central nervous system

EAE:

Experimental autoimmune encephalomyelitis

HLA:

Human leukocyte antigen

MBP:

Myelin basic protein

MHC:

Major histocompatibility complex

MMP:

Matrix metalloproteinase

MOG:

Myelin oligodendrocyte glycoprotein

MS:

Multiple sclerosis

NAWM:

Normal appearing white matter

PADs:

Peptidylarginine deiminases

PBMCs:

Peripheral blood mononuclear cells

PLP:

Proteolipid protein

PTMs:

Posttranslational modifications

RA:

Reheumatoid arthritis

TCR:

T cell receptor

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Acknowledgments

The authors are grateful to Yi-fan Du, department of medical imaging, Dalian Medical University for producing Fig. 1.

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Authors and Affiliations

  1. Department of Physiology, Dalian Medical University, Dalian, China

    Lei Yang, Dewei Tan & Hua Piao

  2. Department of Medical Imaging, Dalian Medical University, Dalian, China

    Lei Yang

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  1. Lei Yang
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  2. Dewei Tan
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  3. Hua Piao
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Correspondence to Hua Piao.

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Yang, L., Tan, D. & Piao, H. Myelin Basic Protein Citrullination in Multiple Sclerosis: A Potential Therapeutic Target for the Pathology. Neurochem Res 41, 1845–1856 (2016). https://doi.org/10.1007/s11064-016-1920-2

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  • DOI: https://doi.org/10.1007/s11064-016-1920-2

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