myelin-basic-protein and leupeptin

Autoantibodies from autistic spectrum disorder (ASD) patients react with multiple proteins expressed in the brain. One such autoantibody targets myelin basic protein (MBP). ASD patients have autoantibodies to MBP of both the IgG and IgA classes in high titers, but no autoantibodies of the IgM class. IgA autoantibodies act as serine proteinases and degrade MBP in vitro. They also induce a decrease in long-term potentiation in the hippocampi of rats either perfused with or previously inoculated with this IgA. Because this class of autoantibody causes myelin sheath destruction in multiple sclerosis (MS), we hypothesized a similar pathological role for them in ASD.

Topics: Adolescent; Animals; Autistic Disorder; Brain; Child; Child, Preschool; Cysteine Proteinase Inhibitors; Dose-Response Relationship, Drug; Female; Hippocampus; Humans; Immunoglobulin A; In Vitro Techniques; Leupeptins; Long-Term Potentiation; Male; Myelin Basic Protein; Patch-Clamp Techniques; Proteolysis; Rats; Rats, Sprague-Dawley; Synaptic Transmission

Myelin basic protein (MBP) extracted from human delipidated white matter was found to be degraded at pH 3.0 by endogenous proteolytic activities of extracts. Electrophoretic peptide patterns were consistent with limited proteolysis of MBP. Based on pH, activation by EDTA and DTE, and inhibition by p-CMPS, E-64 and, in particular, by leupeptin, the protease involved was tentatively identified as cathepsin B or a cathepsin B-like enzyme. As pepstatin failed to inhibit acid proteolysis of MBP cathepsin D was ruled out.

Topics: 4-Chloromercuribenzenesulfonate; Cathepsin B; Cathepsins; Dithioerythritol; Edetic Acid; Electrophoresis, Polyacrylamide Gel; Humans; Hydrogen-Ion Concentration; Leucine; Leupeptins; Myelin Basic Protein; Protease Inhibitors