Lipids in Multiple Sclerosis
Increasing evidence suggests that lipids antigens may be target of autoimmune attacks in inflammatory diseases of the central nervous system. Preliminary observations in multiple sclerosis and in experimental autoimmune encephalomyelitis indicate that bot
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Lipids in Multiple Sclerosis
L. Rinaldi . F. Grassivaro . P. Gallo
1 Lipids in the Myelin Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 594 2 Exogenous Glycolipid Antigens and Autoimmunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 595 3 Glycolipids and Autoimmune Demyelination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 595 4 Sulfatides in EAE and MS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 597 5 Sphingolipids and Autoimmunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 597 6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 598
G. Tettamanti & G. Goracci (eds.), Neural Lipids, DOI 10.1007/978-0-387-30378-9_24, # Springer ScienceþBusiness Media, LLC 2009
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Lipids in multiple sclerosis
Abstract: Increasing evidence suggests that lipids antigens may be target of autoimmune attacks in inflammatory diseases of the central nervous system. Preliminary observations in multiple sclerosis and in experimental autoimmune encephalomyelitis indicate that both T cell and antibody reactivity to structural lipids of myelin may play a role in determining autoimmune-mediated demyelination. Molecular mimicry between bacterial and myelin glycolipids has been observed, and a subset of NKT cells specific for glycolipid antigens has been identified. Increased sulfatide-reactive T-cells and antibodies were demonstrated in multiple sclerosis patients. The possibility that myelin lipids may be targets for autoimmune reactions in central nervous system diseases opens new research and therapeutic perspectives for multiple sclerosis. List of Abbreviations: (APC), antigen presenting cells; (EAE), experimental autoimmune encephalomyelitis; (IFN), interferon; (LPA), lysophosphatidic acid; (MHC-I), major histocompatibility complex class I; [MBP], myelin basic protein; [MOG], myelin oligodendrocyte protein; (NOD), non-obese diabetic; (OPC), oligodendrocyte progenitor cell; [PLP], proteolipid protein; (TCR), T cell receptor; (TNF), tumor necrosis factor
1 Lipids in the Myelin Structure The myelin sheath is formed by extensions of oligodendrocyte cell membranes that wrap around the axon to form a cylindrical coating a few tens of micrometers in diameter (Boggs and Moscarello, 1978; Morell and Norton, 1980). The sheath consists of repeat units of ‘‘double’’ bilayers separated by 3- to 4-nm-thick aqueous layers that alternate between the cytoplasmic and extracellular spaces (Boggs and Moscarello, 1978). Seventy to eighty percent of the dry weight of myelin consists of lipids, a proportion that is signi
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