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Initiation and propagation of neurodegeneration

Nature Medicine volume 16, pages 1201–1204 (2010)Cite this article

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Abstract

Although substantial progress has been made in understanding the molecular and pathological bases of neurodegeneration, there have been few successes in the clinic and a number of fundamental questions remain unanswered. Is this skepticism misplaced, or do the words of Sir Isaac Newton hold true, that “what we know is a drop, what we don't know is an ocean”?

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Figure 1: The amyloid cascade hypothesis.

References

  1. Haass, C. EMBO J. 23, 483–488 (2004).

    Article  CAS  Google Scholar 

  2. Rubinsztein, D.C. Nature 443, 780–786 (2006).

    Article  CAS  Google Scholar 

  3. Veeraraghavalu, K., Choi, S.H., Zhang, X. & Sisodia, S.S. J. Neurosci. 30, 6903–6915 (2010).

    Article  CAS  Google Scholar 

  4. Hu, X. et al. Nat. Neurosci. 9, 1520–1525 (2006).

    Article  CAS  Google Scholar 

  5. Willem, M. et al. Science 314, 664–666 (2006).

    Article  CAS  Google Scholar 

  6. Bremer, J. et al. Nat. Neurosci. 13, 310–318 (2010).

    Article  CAS  Google Scholar 

  7. Brown, M.S., Ye, J., Rawson, R.B. & Goldstein, J.L. Cell 100, 391–398 (2000).

    Article  CAS  Google Scholar 

  8. Aguzzi, A. & Haass, C. Science 302, 814–818 (2003).

    Article  CAS  Google Scholar 

  9. Falsig, J. et al. Nat. Neurosci. 11, 109–117 (2008).

    Article  CAS  Google Scholar 

  10. Hardy, J. & Selkoe, D.J. Science 297, 353–356 (2002).

    Article  CAS  Google Scholar 

  11. Iacono, D. et al. Neurology 73, 665–673 (2009).

    Article  CAS  Google Scholar 

  12. Holmes, C. et al. Lancet 372, 216–223 (2008).

    Article  CAS  Google Scholar 

  13. Schenk, D. et al. Nature 400, 173–177 (1999).

    Article  CAS  Google Scholar 

  14. Schenk, D., Hagen, M. & Seubert, P. Curr. Opin. Immunol. 16, 599–606 (2004).

    Article  CAS  Google Scholar 

  15. Haass, C. & Selkoe, D.J. Nat. Rev. Mol. Cell Biol. 8, 101–112 (2007).

    Article  CAS  Google Scholar 

  16. Walsh, D.M. et al. Nature 416, 535–539 (2002).

    Article  CAS  Google Scholar 

  17. Podlisny, M.B. et al. Biochemistry 37, 3602–3611 (1998).

    Article  CAS  Google Scholar 

  18. Lesné, S. et al. Nature 440, 352–357 (2006).

    Article  Google Scholar 

  19. Shankar, G.M. et al. Nat. Med. 14, 837–842 (2008).

    Article  CAS  Google Scholar 

  20. Laurén, J., Gimbel, D.A., Nygaard, H.B., Gilbert, J.W. & Strittmatter, S.M. Nature 457, 1128–1132 (2009).

    Article  Google Scholar 

  21. Calella, A.M. et al. EMBO Mol. Med. 2, 306–314 (2010).

    Article  CAS  Google Scholar 

  22. Gimbel, D.A. et al. J. Neurosci. 30, 6367–6374 (2010).

    Article  CAS  Google Scholar 

  23. Roberson, E.D. et al. Science 316, 750–754 (2007).

    Article  CAS  Google Scholar 

  24. Ittner, L.M. et al. Cell 142, 387–397 (2010).

    Article  CAS  Google Scholar 

  25. Ballatore, C., Lee, V.M. & Trojanowski, J.Q. Nat. Rev. Neurosci. 8, 663–672 (2007).

    Article  CAS  Google Scholar 

  26. de Calignon, A. et al. Nature 464, 1201–1204 (2010).

    Article  CAS  Google Scholar 

  27. Paquet, D. et al. J. Clin. Invest. 119, 1382–1395 (2009).

    Article  CAS  Google Scholar 

  28. Meyer-Luehmann, M. et al. Science 313, 1781–1784 (2006).

    Article  CAS  Google Scholar 

  29. Frost, B., Jacks, R.L. & Diamond, M.I. J. Biol. Chem. 284, 12845–12852 (2009).

    Article  CAS  Google Scholar 

  30. Clavaguera, F. et al. Nat. Cell Biol. 11, 909–913 (2009).

    Article  CAS  Google Scholar 

  31. Kordower, J.H., Chu, Y., Hauser, R.A., Freeman, T.B. & Olanow, C.W. Nat. Med. 14, 504–506 (2008).

    Article  CAS  Google Scholar 

  32. Li, J.Y. et al. Nat. Med. 14, 501–503 (2008).

    Article  CAS  Google Scholar 

  33. Aguzzi, A. & Rajendran, L. Neuron 64, 783–790 (2009).

    Article  CAS  Google Scholar 

  34. Aguzzi, A. Nature 459, 924–925 (2009).

    Article  CAS  Google Scholar 

  35. Chesebro, B. et al. Science 308, 1435–1439 (2005).

    Article  CAS  Google Scholar 

  36. Thal, D.R., Capetillo-Zarate, E., Del Tredici, K. & Braak, H. Sci. SAGE KE 2006, re1 (2006).

    PubMed  Google Scholar 

  37. Fraering, P.C. et al. Biochemistry 43, 9774–9789 (2004).

    Article  CAS  Google Scholar 

  38. Bard, F. et al. Nat. Med. 6, 916–919 (2000).

    Article  CAS  Google Scholar 

  39. Winklhofer, K.F., Tatzelt, J. & Haass, C. EMBO J. 27, 336–349 (2008).

    Article  CAS  Google Scholar 

  40. Keller, J.N., Hanni, K.B. & Markesbery, W.R. J. Neurochem. 75, 436–439 (2000).

    Article  CAS  Google Scholar 

  41. Ravikumar, B., Duden, R. & Rubinsztein, D.C. Hum. Mol. Genet. 11, 1107–1117 (2002).

    Article  CAS  Google Scholar 

  42. Cataldo, A.M., Hamilton, D.J., Barnett, J.L., Paskevich, P.A. & Nixon, R.A. J. Neurosci. 16, 186–199 (1996).

    Article  CAS  Google Scholar 

  43. Lee, J.H. et al. Cell 141, 1146–1158 (2010).

    Article  CAS  Google Scholar 

  44. Baker, M. et al. Nature 442, 916–919 (2006).

    Article  CAS  Google Scholar 

  45. Cruts, M. et al. Nature 442, 920–924 (2006).

    Article  CAS  Google Scholar 

  46. Rohrer, J.D. et al. Neuroimage published online, 10.1016/j.neuroimage.2009.12.088 (4 January 2010).

  47. Dormann, D. et al. EMBO J. 29, 2841–2857 (2010).

    Article  CAS  Google Scholar 

  48. Kwiatkowski, T.J. Jr. et al. Science 323, 1205–1208 (2009).

    Article  CAS  Google Scholar 

  49. Vance, C. et al. Science 323, 1208–1211 (2009).

    Article  CAS  Google Scholar 

  50. Di Monte, D.A., Lavasani, M. & Manning-Bog, A.B. Neurotoxicology 23, 487–502 (2002).

    Article  CAS  Google Scholar 

  51. Lazarov, O. et al. Cell 120, 701–713 (2005).

    Article  CAS  Google Scholar 

  52. Kang, J.E. et al. Science 326, 1005–1007 (2009).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This article reports on some of the main points raised at the Herrenhausen Symposium on Neurodegeneration in Seeon, Germany (May 2010) during the session on the initiation and propagation of neurodegeneration. I thank A. Aguzzi, D. Rubinsztein, S. Sisodia, D. Edbauer and M. Meyer-Lühmann for reading this manuscript. This work was supported by the Deutsche Forschungsgemeinschaft.

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Authors and Affiliations

  1. DZNE—German Center for Neurodegenerative Diseases, Munich, Germany

    Christian Haass

  2. Adolf-Butenandt-Institute, Biochemistry, Ludwig-Maximilians-University, Munich, Germany

    Christian Haass

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  1. Christian Haass
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Correspondence to Christian Haass.

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Haass, C. Initiation and propagation of neurodegeneration. Nat Med 16, 1201–1204 (2010). https://doi.org/10.1038/nm.2223

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