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Molecular and immunogenic features of myelin lipids: incitants or modulators of multiple sclerosis?

Department of Neurology, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia, USA; Department of Immunochemistry, Ludwik Hirszfeld Institute of Immunology & Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla Wroclaw, Poland

EL Hogan

Department of Neurology, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia, USA; Department of Microbiology, National University of Ireland Galway, University Road, Galway, Irelandehogan{at}mail.mcg.edu

Myelin lipids have long been thought to play intriguing roles in the pathogenesis of multiple sclerosis (MS). This review summarizes current understanding of the molecular basis of MS with emphasis on the: (i.) physico-chemical properties, organization and accessibility of the lipids and their distribution within the myelin multilayer; (ii.) characterization of myelin lipid structures, and structure–function relationships relevant to MS mechanisms, and; (iii.) immunogenic and other features of lipids in MS including molecular mimicry, lipid enzyme genetic knockouts, glycolipid-reactive NKT cells, and monoclonal antibody-induced remyelination. New findings associate anti-lipid antibodies with pathophysiological biomarkers and suggest clinical utility. The structure of CD1d-lipid complexed with the lipophilic invariant T cell receptor (iTCR) may be crucial to understanding MS pathogenesis, and design of lipid antigen-specific therapeutics. Novel immuno-modulatory tools for treatment of autoimmune diseases including MS in which there is both constraint of inflammation and stimulation of remyelination are now emerging.

Key Words: gangliosides • glycolipids • multiple sclerosis • myelin • phospholipids • sulfatide

Multiple Sclerosis, Vol. 15, No. 9, 1011-1029 (2009)
DOI: 10.1177/1352458509106708


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