Cellular and molecular mechanisms of autoimmune demyelination in the central nervous system

Experimental autoimmune encephalomyelitis (EAE), particularly in its chronic form, shares features with the major human demyelinating disease multiple sclerosis (MS). The roles of lymphocytes and antigen-presenting cells in EAE are increasingly clear. However, little information has been collated on the molecular events involving myelin components in the initiation and perpetuation of the autoimmune condition and in demyelination itself. To draw together relevant data, this review first outlines the molecular structure of the myelin sheath. Evidence implicating individual myelin molecules, as autoimmunogens, as targets for autoimmune attack, or as participants in the demyelinating processes in EAE, is then discussed. Finally, the extent to which the experimental findings are mirrored in MS, and the natural genesis of myelin-directed autoimmunity are considered.