Structure and function of the myelin proteins: current status and perspectives in relation to multiple sclerosis.
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 neuroantigen-specific 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.
Tzakos
Andreas G
AG
Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, Ioannina GR-45110, Greece.
Troganis
Anastassios
A
Theodorou
Vassiliki
V
Tselios
Theodore
T
Svarnas
Christos
C
Matsoukas
John
J
Apostolopoulos
Vasso
V
Gerothanassis
Ioannis P
IP
D000595:Amino Acid Sequence; D002490:Central Nervous System / Q000378:metabolism*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000378:metabolism*; D009185:Myelin Proteins / Q000737:chemistry / Q000378:metabolism*; D009186:Myelin Sheath / Q000737:chemistry / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D013329:Structure-Activity Relationship
D000939:Epitopes; D006680:HLA Antigens; D008055:Lipids; D009185:Myelin Proteins; D011948:Receptors, Antigen, T-Cell