CELLULAR AND MOLECULAR APPROACHES TO NEUROTOXICOLOGY

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Neurotoxins are known to disrupt the structure of myelin. The membranes of this ubiquitous material of the nervous system contain three major proteins. Myelin basic protein, which accounts for 30 percent of CNS myelin proteins, has no known physiological function, although injection of purified MBP will cause Experimental Allergic Encephalomyelitis, considered by some as a model for Multiple Sclerosis. A molecular model for the structure of MBP generates a series of testable predictions. We have been examining the structural properties of MBP using fluorescence and optical spectroscopy. Contrary to many reports, we find evidence for extensive long range structural specificity of MBP in agreement with the model. We find that a subfraction of isolated MBP molecules bind heme and other porphyrins with affinities on the order of 10-8 M. These molecules also bind ANS derivatives with affinities on the order of 10-7 M. Heme rapidly displaces bound bis-ANS. These studies may lead to a rapid, more precise functional assay for MBP than the induction of EAE.