The Myelin Membrane and Its Basic Proteins
Peripheral nerve myelin contains a wider variety of protein components than central nervous system myelin. Common features are the presence of the basic Al protein, as shown by amino acid sequence, and a high proportion of a hydrophobic protein such as the PO protein (PNS) and the FL proteolipid (CNS) which are likely amphipathic components. It was proposed that the Al protein only partially penetrates into the lipid layer and thus is externally situated such that it can provide a structural security in the lateral dimension. The hydrophobic proteins may provide a vertical (radial) stabilization to myelin via linear polymerization across the lammelae layers. The PNS and CNS myelin also differ in immunologic properties since the Al protein, which induces allergic emcephalomyelitis in animals when given alone or as part of CNS myelin, is masked in PNS myelin. By contrast, PNS myelin induces allergic neuritis in monkeys where the responsible antigen appears to be the P2 protein, a basic protein absent in CNS myelin. The rabbit P2 protein (12,000 MW) is a more compact, highly structured molecule in contrast to the open, extended double-chain conformation of the Al protein (18,000 MW).
The role of these proteins in human demyelination diseases appears crucial. Guillian-Barre patients show a cellular hypersensitivity to the P2 protein; multiple sclerosis (MS) subjects show a hypersensitivity to the Al protein prior to and during exacerbation. These data suggest that allergic encephalomyelitis and neuritis are relevant animal models for early phases of the respective human disease, and provide a rationale for consideration of clinical studies aimed to suppress MS; in monkeys with severe clinical signs of allergic encephalomyelitis, the Al protein was shown to suppress and reverse the course of the disease.
KeywordsMultiple Sclerosis Basic Protein Myelin Protein Myelin Membrane Multiple Sclerosis Subject
Unable to display preview. Download preview PDF.
- 2.Finear, J.B., Ann. N.Y. Acad. Sci., 122, 51, 1965.Google Scholar
- 3.Davison, A.N. in Myelination (Davison, A., and Peters, A.), p. 90, Charles Thomas, Springfield, Ill., 1970.Google Scholar
- 4.Eylar, E.H. in Functional and Structural Proteins of the Nervous System ( Davison, A., Mandel, P., and Morgan, I., eds.) p. 215–239, Plenum Press, New York, 1972.Google Scholar
- 5.Suzuki, K., Poduslo, S., and Norton, W.T., Biochim. Biophys. Acta, 144, 375, 1967.Google Scholar
- 6.Quarles, R., Everly, J. and Brady, R., J. Neurochem, 21, 1177, 19730Google Scholar
- 10.Eylar, J.H., in Multiple Sclerosis ( Wolfgram, F., Ellison, G., Stevens, J., and Andrews, J., eds), p. 449–481, Acad. Press, New York, 1972 ).Google Scholar
- 11.Ishaque, A., Roomi, W., and Eylar, E.H., to be published.Google Scholar
- 12.Agrawal, H.C., Burton, R., Fishman, M., Mitchell, R., and Prensky, A., J. Neurochem, 19, 2083, 1972.Google Scholar
- 25.London, Y., Demel, R, R., Kessel, G., Vossenberg, F., and van Deenen, L., Biochim. Biophys. Acta, 311, 520, 1973Google Scholar
- 28.Rauch,H., and Einstein, E.R., Rev. Neuroscience, I, 283, 1974.Google Scholar
- 32.Wood. D., Vail, W., amd Moscarello, M., Brain Res. 93, 463, 1975.Google Scholar
- 34.Laatsch,R., Kies, M., Gordon, S., and Alvord, E.C., J. Exp. Med., 115, 778, 1962.Google Scholar
- 36.Arnason, B., Asbury, A., Astrom, K., and Adams, R., Trans. Am. Neurol. Assoc. 93, 133, 1968.Google Scholar
- 40.News and Views, Nature, 260, 190, 1976.Google Scholar
- 42.Sheremata, W., Cosgrove, J., and Eylar, E.H., J. Neuro. Sc., in press.Google Scholar
- 43.Sheremata, W., Cosgrove, J., and Eylar, E.H., Trans. Am. Neurol. Assoc. 99, 49, 1974.Google Scholar
- 44.Sheremata, W., and Eylar, E.H., 5th Int. Cong. Neurochem, Barcelona, 1975.Google Scholar
- 46.Utermohlen, W., and Zabriskie, Lancet, 2, 1147, 1973.Google Scholar
- 47.Jersild, C., Dupont, B., Fog, T., Hansen,G., Neilsen, L., Thomsen, M., and Svejgaard, A., Transplant. Proc. V, 1791, 1973.Google Scholar