Current Medicinal Chemistry

Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK

Back

Structure and Function of the Myelin Proteins: Current Status and Perspectives in Relation to Multiple Sclerosis

Author(s): Andreas G. Tzakos, Petri Kursula, Anastassios Troganis, Vassiliki Theodorou, Theodore Tselios, Christos Svarnas, John Matsoukas, Vasso Apostolopoulos and Ioannis P. Gerothanassis

Affiliation: Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina,Ioannina GR-45110, Greece.

Abstract:

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination and loss of neurological function, local macrophage infiltrate and neuroantigenspecific CD4+T cells. MS arises from complex interactions between genetic, immunological, infective and biochemical mechanisms. Although the circumstances of MS etiology remain hypothetical, one persistent theme involves immune system recognition of myelin-specific antigens derived from myelin basic protein, the most abundant extrinsic myelin membrane protein, and/or another equally suitable myelin protein or lipid. Knowledge of the biochemical and physico-chemical properties of myelin proteins and lipids, particularly their composition, organization, structure and accessibility with respect to the compacted myelin multilayers, becomes central to understanding how and why myelin-specific antigens become selected during the development of MS. This review focuses on the current understanding of the molecular basis of MS with emphasis: (i) on the physical-chemical properties, organization, morphology, and accessibility of the proteins and lipids within the myelin multilayers; (ii) on the structure-function relationships and characterization of the myelin proteins relevant to the manifestation and evolution of MS; (iii) on conformational relationships between myelin epitopes which might become selected during the development of MS; (iv) on the structure of MHC/HLA in complex with MBP peptides as well as with TCR, which is crucial to the understanding of the pathogenesis of MS with the ultimate goal of designed antigen-specific treatments.

Keywords: multiple sclerosis, proteins of the myelin sheath, mbp, mhc, tcr, docking, epitopes, structure

Order Reprints Order Eprints Rights & PermissionsPrintExport

Article Details

VOLUME: 12
ISSUE: 13
Page: [1569 - 1587]
Pages: 19
DOI: 10.2174/0929867054039026
Price: $58