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Letters in Peptide Science

, Volume 10, Issue 5–6, pp 413–417 | Cite as

Methionine oxidation: Implications for the mechanism of toxicity of the β-amyloid peptide from Alzheimer's disease

  • Giuseppe D. Ciccotosto
  • Kevin J. Barnham
  • Robert A. Cherny
  • Colin L. Masters
  • Ashley I. Bush
  • Cyril C. Curtain
  • Roberto Cappai
  • Deborah Tew
Article

Summary

The amyloid β-peptide, Aβ is toxic to neurons and this toxicity plays a central role in the progression of Alzheimer's disease. The mechanism(s) by which Aβ exerts its toxicity has been hotly debated with several theories postulated. Here we discuss the role of oxidation of the sulfur atom of Met35 in Aβ42 (Met(O)Aβ), a modification that has significant implications for the mechanism of Aβ toxicity. Both Met(O)Aβ and its native form display toxicity to primary neuronal cells in culture which can be rescued by catalase, a H2O2 inhibitor and clioquinol a mild copper chelator. However both native Aβ and Met(O)Aβ differ substantially in primary and secondary structures, solubility, ability to penetrate lipid membranes, and oligomerization profiles. It is clearly evident that metals play an important role in the oxidation of Aβ to Met(O)Aβ via Fenton chemistry and that regulation of this pathway has a potential therapeutic application for the regulation of Alzheimer's disease.

Key words

Alzheimer's disease amyloid beta copper oxidation toxicity 

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References

  1. 1.
    Hardy, J., Trends in Neurosci., 20 (1997) 154.CrossRefGoogle Scholar
  2. 2.
    Selkoe, D.J., Physiol. Rev., 81 (2001) 741.PubMedGoogle Scholar
  3. 3.
    McLean, C.A., Cherny, R.A., Fraser, F.W., Fuller, S.J., Smith, M.J., Beyreuther, K., Bush, A.I. and Masters, C.L., Ann. Neurol. 46 (1999) 860.PubMedCrossRefGoogle Scholar
  4. 4.
    Harkany, T., Hortobágyi, T., Sasvári, M., Kónya, C., Penke, B., Luiten, P.G.M. and Nyakas, C., Prog. Neuro-Psychopharmacol. Biol. Psychiat. 23 (1999) 963.CrossRefGoogle Scholar
  5. 5.
    Yankner, B.A., Duffy, L.K. and Kirschner, D.A., Science, 250 (1990) 279.PubMedGoogle Scholar
  6. 6.
    Walsh, D.M., Klyubin, I., Fadeeva, J.V., Cullen, W.K., Anwyl, R., Wolfe, M.S., Rowan, M.J. and Selkoe, D.J., Nature, 416 (2002) 535.PubMedCrossRefGoogle Scholar
  7. 7.
    Barnham, K.J., Ciccotosto, G.D., Tickler, A.K., Ali, F.E., Smith, D.G., Williamson, N.A., Lam, Y.H., Carrington, D., Tew, D., Kocak, G., Volitakis, I., Separovic, F., Barrow, C.J., Wade, J.D., Masters, C.L., Cherny, R.A., Curtain, C.C., Bush, A.I. and Cappai, R. J. Biol. Chem., 278 (2003) 42959.PubMedCrossRefGoogle Scholar
  8. 8.
    Varadarajan, S., Yatin, S., Kanski, J., Jahanshahi, F. and Butterfield, D.A., Brain. Res. Bull., 50 (1999) 133.PubMedCrossRefGoogle Scholar
  9. 9.
    Varadarajan, S., Kanski, J., Aksenova, M., Lauderback, C. and Butterfield, D.A., J. Am. Chem. Soc.,123 (2001) 5625.PubMedCrossRefGoogle Scholar
  10. 10.
    Harper, J.D., Wong, S.S., Lieber, C.M. and Lansbury, P.T., Biochemistry, 38 (1999) 8972.PubMedCrossRefGoogle Scholar
  11. 11.
    Lorenzo, A. and Yankner, B.A., Proc. Natl. Acad. Sci. USA, 91 (1994), 12243.PubMedCrossRefGoogle Scholar
  12. 12.
    Pike, C.J., Burdick, D., Walencewicz, A.J., Glabe, C.G. and Cotman, C.W., J. Neurosci., 13 (1993) 1676PubMedGoogle Scholar
  13. 13.
    Bitan, G., Tarus, B., Vollers, S.S., Lashuel, H.A., Condron, M.M., Straub, J.E. and Teplow, D.B., J. Am. Chem. Soc., 125 (2003) 15359.PubMedCrossRefGoogle Scholar
  14. 14.
    Hou, L., Kang, I., Marchant, R.E. and Zagorski, M.G., J. Biol. Chem., 277 (2002) 40173.PubMedCrossRefGoogle Scholar
  15. 15.
    Cherny, R.A., Atwood, C.S., Xilinas, M.E., Gray, D.N., Jones, W.D., McLean, C.A., Barnham, K.J., Volitakis, I., Fraser, F.W., Kim, Y., Huang, X., Goldstein, L.E., Moir, R.D., Lim, J.T., Beyreuther, K., Zheng, H., Tanzi, R.E., Masters, C.L. and Bush, A.I., Neuron, 30 (2001) 665.PubMedCrossRefGoogle Scholar
  16. 16.
    Ritchie, C.W., Bush, A.I., Mackinnon, A., Macfarlane, S., Mastwyk, M., MacGregor, L., Kiers, L., Cherny, R.A., Li, Q.-X., Tammer, A., Carrington, D., Mavros, C., Volitakis, I., Xilinas, M., Ames, D., Davis, S., Beyreuther, K., Tanzi, R.E. and Masters, C.L., Arch. Neurol., (2003) 1685.Google Scholar
  17. 17.
    Lee, J.Y., Cole, T.B., Palmiter, R.D., Suh, S.W., and Koh, J.Y., Proc. Natl. Acad. Sci. USA, 99 (2002), 7705.PubMedCrossRefGoogle Scholar
  18. 18.
    Muller, W.E., Kirsch, C. and Eckert, G.P., Biochem. Soc. Trans., 29 (2001) 617.PubMedCrossRefGoogle Scholar
  19. 19.
    Hartmann, H., Eckert, A. and Muller, W.E., Life Sci., 55 (1994) 2011.PubMedCrossRefGoogle Scholar
  20. 20.
    Kourie, J.I., Cell Mol. Neurobiol., 21 (2001), 173.PubMedCrossRefGoogle Scholar
  21. 21.
    Durell, S.R., Guy, H.R., Arispe, N., Rojas, E. and Pollard, H.B., Biophys. J., 67 (1994) 2137.PubMedCrossRefGoogle Scholar
  22. 22.
    Arispe, N., Rojas, E. and Pollard, H.B., Proc. Natl. Acad. Sci. USA, 90 (1993) 567.PubMedCrossRefGoogle Scholar
  23. 23.
    Butterfield, D.A., Drake, J., Pocernich, C. and Castegna, A., Trends Mol. Med., 7 (2001) 548.PubMedCrossRefGoogle Scholar
  24. 24.
    Varadarajan, s., Yatin, S., Aksenova, M. and Butterfield, D.A., J. Struct. Biol., 130 (2000), 184.PubMedCrossRefGoogle Scholar
  25. 25.
    Pratico, D., Clark, C.M., Lee, V.M., Trojanowski, J.Q., Rokach, J. and FitzGerald, G.A., Ann. Neurol., 48 (2000) 809.PubMedCrossRefGoogle Scholar
  26. 26.
    Pratico, D., Uryu, K., Leight, S., Trojanoswki, J.Q. and Lee, V.M., J. Neurosci., 21 (2001) 4183.PubMedGoogle Scholar
  27. 27.
    Hartmann, H., Eckert, A. and Muller, W.E., Biochem. Biophys. Res. Commun., 194 (1993) 1216.PubMedCrossRefGoogle Scholar
  28. 28.
    Kawahara, M., Kuroda, Y., Arispe, N. and Rojas, E., J. Biol. Chem., 275 (2000) 14077.PubMedCrossRefGoogle Scholar
  29. 29.
    Curtain, C.C., Ali, F., Volitakis, I., Cherny, R.A., Norton, R.S., Beyreuther, K., Barrow, C.J., Masters, C.L., Bush, A.I. and Barnham, K.J., J. Biol. Chem., 276 (2001) 20466.PubMedCrossRefGoogle Scholar
  30. 30.
    Curtain, C.C., Ali, F.E., Smith, D.G., Bush, A.I., Masters, C.L. and Barnham, K.J., J. Biol. Chem., 278 (2003) 2977.PubMedCrossRefGoogle Scholar
  31. 31.
    Miura, T., Suzuki, K., Kohata, N. and Takeuchi, H., Biochemistry, 39 (2000) 7024.PubMedCrossRefGoogle Scholar
  32. 32.
    Cuajungco, M.P., Goldstein, L.E., Nunomura, A., Smith, M.A., Lim, J.T., Atwood, C.S., Huang, X., Farrag, Y.W., Perry, G. and Bush, A.I., J. Biol. Chem., 275 (2000) 19439.PubMedCrossRefGoogle Scholar
  33. 33.
    Huang, X., Atwood, C.S., Hartshorn, M.A., Multhaup, G., Goldstein, L.E., Scarpa, R.C., Cuajungco, M.P., Gray, D.N., Lim, J., Moir, R.D., Tanzi, R.E. and Bush, A.I., Biochemistry, 38 (1999) 7609.PubMedCrossRefGoogle Scholar
  34. 34.
    Huang, X., Cuajungco, M.P., Atwood, C.S., Hartshorn, M.A., Tyndall, J.D., Hanson, G.R., Stokes, K.C., Leopold, M., Multhaup, G., Goldstein, L.E., Scarpa, R.C., Sauders, A.J., Lim, J., Moir, R.D., Glabe, C., Bowden, E.F., Masters, C.L., Fairlie, D.P., Tanzi, R.E. and Bush, A.I., J. Biol. Chem., 274 (1999) 37111.PubMedCrossRefGoogle Scholar
  35. 35.
    Nishino, S. and Nishida, Y., Inorg. Chem. Commun., 4 (2001) 86.CrossRefGoogle Scholar
  36. 36.
    Naslund, J., Schierhorn, A., Hellman, U., Lannfelt, L., Roses, A.D., Tjernberg, L.O., Silberring, J., Gandy, S.E., Winblad, B., Greengard, P. andet al. Proc. Natl. Acad. Sci. USA, 91 (1994) 8378.PubMedCrossRefGoogle Scholar
  37. 37.
    Kuo, Y.M., Kokjohn, T.A., Beach, T.G., Sue, L.I., Brune, D., Lopez, J.C., Kalback, W.M., Abramowski, D., Sturchler-Pierrat, C., Staufenbiel, M. and Roher, A.E., J. Biol. Chem., 276 (2001) 12991.PubMedCrossRefGoogle Scholar
  38. 38.
    Sayre, L.M., Perry, G., Harris, P.L., Liu, Y., Schubert, K.A. and Smith, M.A., J. Neurochem., 74 (2000) 270.PubMedCrossRefGoogle Scholar
  39. 39.
    Schoneich, C. Arch. Biochem. Biophys., 397 (2002) 370.PubMedCrossRefGoogle Scholar
  40. 40.
    Yatin, S.M., Varadarajan, S., Link, C.D. and Butterfield, D.A., Neurobiol. Aging., 20 (1999), 325; discussion 339.PubMedCrossRefGoogle Scholar
  41. 41.
    Dado, G.P. and Gellman, S.H., J. Am. Chem. Soc., 115 (1993) 12609.CrossRefGoogle Scholar
  42. 42.
    Palmblad, M., Westlind-Danielsson, A. and Bergquist, J., J. Biol. Chem., 277 (2002) 19506.PubMedCrossRefGoogle Scholar
  43. 43.
    Opazo, C., Huang, X., Cherny, R.A., Moir, R.D., Roher, A.E., White, A.R., Cappai, R., Masters, C.L., Tanzi, R.E., Inestrosa, N.C. and Bush, A.I., J. Biol. Chem., 277 (2002) 40302.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Giuseppe D. Ciccotosto
    • 1
    • 2
  • Kevin J. Barnham
    • 1
    • 2
  • Robert A. Cherny
    • 1
    • 2
  • Colin L. Masters
    • 1
    • 2
  • Ashley I. Bush
    • 1
    • 3
    • 2
  • Cyril C. Curtain
    • 1
    • 4
    • 2
  • Roberto Cappai
    • 1
    • 2
  • Deborah Tew
    • 1
    • 2
  1. 1.Department of PathologyThe University of Melbourne
  2. 2.The Mental Health Research Institute of VictoriaParkvilleAustralia
  3. 3.Laboratory for Oxidation Biology, Genetics and Aging Unit and Department of Psychiatry, Harvard Medical SchoolMassachusetts General Hospital EastCharlestownUSA
  4. 4.School of Physics and Materials EngineeringMonash UniversityAustralia

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