The misconstruction of
proteins as a result of the displacement of one of more
proline residues by their congener,
azetidine-2-carboxylic acid (Aze), can result in various disorders. A number of lines of evidence suggest that
multiple sclerosis may be among these. This concept adheres to the current view that
multiple sclerosis lesions originate in the myelin sheath and that the underlying molecular abnormality involves the
myelin basic protein. The Aze hypothesis posits that
myelin basic protein and possibly other closely related molecules are misassembled in sites of lesion formation because of the substitution of Aze for one or more prolines within consensual
epitopes. These include a highly conserved
myelin basic protein hexapeptide sequence, PRTPPP, and an alpha helix bounded by prolyls. Recent studies have focused on the immunopathogenetic effects of posttranslational modification of this region. This hypothesis proposes that the domain is structurally, functionally, and antigenically altered by the intrusion of Aze in place of
proline and that such misassembly may involve other
proteins and adversely affect interactions with neighboring molecules. This report reviews evidence supporting the hypothesis that ingestion of Aze in the diet, in conjunction with
genetic susceptibility, may predispose or contribute to the pathogenesis of
multiple sclerosis.