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Treatment of experimental allergic encephalomyelitis with an inhibitor of cathepsin D (pepstatin)

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Abstract

Intraperitoneal administration of pepstatin (2 mg/day for 5 weeks) to Lewis rats subjected to experimental allergic encephalomyelitis (EAE) (induced by guinea pig spinal cord and pertussis vaccine) suppressed the appearance of clinical signs of disease, and reduced the severity and incidence of CNS lesions normally associated with this disease. Administration of pepstatin for shorter periods to Lewis rats, or BSVS mice, or guinea pigs challenged with myelin basic protein delayed, but did not prevent clinical signs of EAE, but was accompanied in all cases by a less severe histopathology.

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References

  1. Alvord, E. C., Shaw, C. M., Hruby, S., andKies, M. W. 1965. Encephalitogen-induced inhibition of EAE: Prevention, suppression and therapy. Ann. N. Y. Acad. Sci. 122:333–345.

    Google Scholar 

  2. Driscoll, B. F., Kies, M. W., andAlvord, E. C. Jr. 1974. Successful treatment of experimental allergic encephalomyelitis (EAE) in guinea pigs with homologous myelin basic protein. J. Immunol. 112:392–397.

    Google Scholar 

  3. Levine, S., Sowinski, R., andKies, M. W. 1972. Treatment of experimental allergic encephalomyelitis with encephalitogenic basic proteins (36174). Proc. Soc. Exp. Biol. Med. 139:506–510.

    Google Scholar 

  4. Hashim, G. A., andSchilling, F. J. 1973. Prevention of experimental allergic encephalomyelitis by nonencephalitogenic basic peptides. Arch. Biochem. 156:287–297.

    Google Scholar 

  5. Paterson, P. Y., andHanson, M. A. 1969. Studies of cyclophosphamide suppression of EAE in Wistar rats. J. Immunol. 103:795–803.

    Google Scholar 

  6. Boehme, D. H., Fordice, M. W., andMarks, N. 1974. Proteolytic activity in brain and spinal cord in sensitive and resistant strains of rat and mouse subjected to experimental allergic encephalomyelitis. Brain Res. 75:153–162.

    Google Scholar 

  7. Marks, N., Grynbaum, A., andLevine, S. 1977. Proteolytic enzymes in ordinary, hyperacute, monocytic and passive transfer forms of experimental allergic encephalomyelitis. Brain Res. 123:147–157.

    Google Scholar 

  8. Smith, M. 1977. The role of proteolytic enzymes in demyelination in EAE. Neurochem. Res. 2:233–246.

    Google Scholar 

  9. Umezawa, H., andAoyagi, T. 1977. Activities of proteinase inhibitors of microbial origin. Res. Monographs in Cell and Tissue Physiology 2:637–662. elsevier, North-Holland, Amsterdam.

    Google Scholar 

  10. Marks, N., Grynbaum, A., andLajtha, A. 1973. Pentapeptide (pepstatin) inhibition of brain acid proteinase. Science 181:949–951.

    Google Scholar 

  11. Marks, N., Grynabaum, A., andLajtha, A. 1976. The breakdown of myelin-bound proteins by intra- and extracellular proteases. Neurochem. Res. 1:93–111.

    Google Scholar 

  12. Marks, N., D'Monte, B., andLajtha, A. 1973. Inhibition of cerebral proteolytic enzymes. Texas Reports Biol. Med. 31:345–365.

    Google Scholar 

  13. Benuck, M., Marks, N., andHashim, G. 1975. Metabolic instability of myelin proteins: Breakdown of basic protein induced by brain cathepsin D. Eur. J. Biochem. 52:615–621.

    Google Scholar 

  14. Dean, R. T. 1975. Direct evidence of importance of lysosomes in degradation of intracellular proteins. Nature 257:414–416.

    Google Scholar 

  15. Miyamoto, M., Terayama, H., andOhnishi, T. 1973. Effects of protease inhibitors on liver regeneration. Biochem. Biophys. Res. Comm. 55:84–90.

    Google Scholar 

  16. Bazin, S., Mady, L. L., andDelaney, A. 1975. Cathepsin D and catabolism of proteoglycans in granulation tissue. C.R. Hebd. Seances. Acad. Sci. Ser D., 280:1927–1929.

    Google Scholar 

  17. Dingle, J. T., Barrett, A. J., andPoole, A. R. 1972. Inhibition by pepstatin of human cartilage degradation. Biochem. J. 127:443–447.

    Google Scholar 

  18. Arnason, B. G. W. 1972. Immunosuppression in experimental demyelinating diseases. Pages 487–509,In Wolfgram, R., Ellison, G. W., Stevens, V. G., and Andrews, J. M. (eds.) Multiple Sclerosis—Immunology Virology and Ultrastructure. Academic Press, New York.

    Google Scholar 

  19. Hashim, G., Shapre, R., Carvalho, E., andStevens, L. E. 1976. Suppression and reversal of EAE in guinea pigs with a nonencephalitogenic analog of the Trp region of the myelin basic protein. J. Immunol. 116:126–130.

    Google Scholar 

  20. Hashim, G. Myelin basic protein: Structure, function, and antigenic determinants. Immunol. Rev. 39 (in press).

  21. Swanborg, R. H. 1975. Antigen-induced inhibition of EAE. J. Immunol. 114:191–194.

    Google Scholar 

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Authors and Affiliations

  1. Veterans Administration Hospital, East Orange, 07019, New Jersey

    D. H. Boehme

  2. Institute ofMicrobial Chemistry, Tokyo, Japan

    H. Umezawa

  3. St. Lukes Hospital Medical Center, 10025, New York, New York

    G. Hashim

  4. Institute of Neurochemistry, 10035, Ward's Island, New York

    Neville Marks

Authors
  1. D. H. Boehme
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  2. H. Umezawa
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  3. G. Hashim
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  4. Neville Marks
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Boehme, D.H., Umezawa, H., Hashim, G. et al. Treatment of experimental allergic encephalomyelitis with an inhibitor of cathepsin D (pepstatin). Neurochem Res 3, 185–194 (1978). https://doi.org/10.1007/BF00964059

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  • DOI: https://doi.org/10.1007/BF00964059

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