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RAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease

Nature volume 382, pages 685–691 (1996)Cite this article

Abstract

Amyloid-beta peptide is central to the pathology of Alzheimer's disease, because it is neurotoxic—directly by inducing oxidant stress, and indirectly by activating microglia. A specific cell-surface acceptor site that could focus its effects on target cells has been postulated but not identified. Here we present evidence that the 'receptor for advanced glycation end products' (RAGE) is such a receptor, and that it mediates effects of the peptide on neurons and microglia. Increased expression of RAGE in Alzheimer's disease brain indicates that it is relevant to the pathogenesis of neuronal dysfunction and death.

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References

  1. Goedert, M. Trends Neurosci. 16, 460–465 (1993).

    Article  CAS  Google Scholar 

  2. Haass, C. & Selkoe, D. Cell 7, 1039–1042 (1994).

    Google Scholar 

  3. Kosik, K. J. Cell. Biol. 127, 1501–1504 (1994).

    Article  CAS  Google Scholar 

  4. Trojanowski, J. & Lee, V. Am. J. Pathol. 144, 449–453 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Koo, E., Park, L. & Selkoe, D. Proc. Natl Acad. Sci. USA 90, 4748–4752 (1993).

    Article  ADS  CAS  Google Scholar 

  6. Yanker, B., Duffy, L. & Kirschner, D. Science 250, 279–282 (1990).

    Article  ADS  Google Scholar 

  7. Davis, J., McMurray, H. & Schubert, D. Biochem. Biophys. Res. Commun. 189, 1096–1100 (1992).

    Article  CAS  Google Scholar 

  8. Pike, C. et al. Neuroscience 13, 1676–1687 (1993).

    Article  CAS  Google Scholar 

  9. Hensley, K. et al. Proc. Natl Acad. Sci. USA 91, 3270–3274 (1994).

    Article  ADS  CAS  Google Scholar 

  10. Behl, C., Davis, J., Lesley, R. & Schubert, D. Cell 77, 817–827 (1994).

    Article  CAS  Google Scholar 

  11. Meda, L. et al. Nature 374, 647–650 (1995).

    Article  ADS  CAS  Google Scholar 

  12. Klegeris, A., Walker, D. & McGeer, P. Biochem. Biophys. Res. Commun. 199, 984–991 (1994).

    Article  CAS  Google Scholar 

  13. Araujo, D. & Cotman, C. Brain Res. 569, 141–145 (1992).

    Article  CAS  Google Scholar 

  14. Joslin, G. et al. J. Biol. Chem. 266, 21897–21902 (1991).

    CAS  PubMed  Google Scholar 

  15. Fraser, P. et al. J. Neurochem. 61, 298–305 (1993).

    Article  CAS  Google Scholar 

  16. Ghiso, J. et al. Biochem. J. 293, 27–30 (1993).

    Article  CAS  Google Scholar 

  17. Kimura, H. & Schubert, D. Proc. Natl Acad. Sci. USA 90, 7508–7512 (1993).

    Article  ADS  CAS  Google Scholar 

  18. Strittmatter, W. et al. Proc. Natl Acad. Sci. USA 90, 1977–1981 (1993).

    Article  ADS  CAS  Google Scholar 

  19. Strittmatter, W. et al. Exp. Neurol. 122, 327–334 (1993).

    Article  CAS  Google Scholar 

  20. Schwarzman, A. Proc. Natl Acad. Sci. USA 91, 8368–8372 (1994).

    Article  ADS  CAS  Google Scholar 

  21. Kisilevsky, R. et al. Nature Med. 1, 143–148 (1995).

    Article  CAS  Google Scholar 

  22. Schmidt, A-M. et al. J. Biol. Chem. 267, 14987–14997 (1992).

    CAS  PubMed  Google Scholar 

  23. Neeper, M. et al. J. Biol. Chem. 267, 14998–15004 (1992).

    CAS  PubMed  Google Scholar 

  24. Hori, O. et al. J. Biol. Chem. 270, 25752–25761 (1995).

    Article  CAS  Google Scholar 

  25. Rauvala, H. & Pihlaskari, R. J. Biol. Chem. 262, 16625–16635 (1987).

    CAS  PubMed  Google Scholar 

  26. Yan, S-D. et al. Proc. Natl Acad. Sci. USA 91, 7787–7791 (1994).

    Article  ADS  CAS  Google Scholar 

  27. Yan, S-D. et al. Nature Med. 1, 693–699 (1995).

    Article  CAS  Google Scholar 

  28. Harris, J. et al. Exp. Neurol. 131, 193–202 (1995).

    Article  CAS  Google Scholar 

  29. Mattson, M. & Goodman, Y. Brain Res. 676, 219–224 (1995).

    Article  CAS  Google Scholar 

  30. Thomas, T. et al. Nature 380, 168–171 (1996).

    Article  ADS  CAS  Google Scholar 

  31. Osborn, L. et al. Cell 59, 1203–1211 (1989).

    Article  CAS  Google Scholar 

  32. Roher, A. et al. J. Biol. Chem. 268, 3072–3083 (1993).

    CAS  PubMed  Google Scholar 

  33. Schmidt, A-M. et al. J. Clin. Invest. 91, 2155–2168 (1993).

    Article  CAS  Google Scholar 

  34. Bocchini, V. et al. J. Neurosci. Res. 31, 616–621 (1992).

    Article  CAS  Google Scholar 

  35. Dickson, D. et al. Glia 7, 75–83 (1993).

    Article  CAS  Google Scholar 

  36. McGeer, P. et al. Glia 7, 84–92 (1993).

    Article  CAS  Google Scholar 

  37. Wautier, J-L. et al. J. Clin. Invest. 97, 238–243 (1996).

    Article  CAS  Google Scholar 

  38. Schmidt, A-M. et al. J. Clin. Invest. 96, 1395–1403 (1995).

    Article  CAS  Google Scholar 

  39. Yan et al. J. Biol. Chem. 269, 9889–9897 (1994).

    CAS  PubMed  Google Scholar 

  40. Rogers, J. et al. Neurology 43, 1609–1611 (1993).

    Article  CAS  Google Scholar 

  41. Breitner, J. et al. Neurology 44, 227–232 (1994).

    Article  CAS  Google Scholar 

  42. Gumkowski, F. et al. Blood Vessels 24, 11–18 (1987).

    CAS  PubMed  Google Scholar 

  43. Yavin, E. & Yavin, Z. J. Cell Biol. 62, 540–546 (1974).

    Article  CAS  Google Scholar 

  44. Dennery, P., Kramer, C. & Alpert, S. Am. J. Respir. Cell Mol. Biol. 3, 137–144 (1990).

    Article  CAS  Google Scholar 

  45. Brett, J. et al. Am. J. Pathol. 143, 1699–1712 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Departments of Pathology, Surgery, Medicine and Physiology, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, New York, 10032, USA

    Shi Du Yan, Xi Chen, Jin Fu, Ming Chen, Huaijie Zhu, David Stern & Ann Marie Schmidt

  2. Sun Health Research Institute, 10515 Santa Fe Drive, Sun City, Arizona, 85372, USA

    Alex Roher

  3. Berlex Biosciences, San Pablo Avenue, Richmond, California, 94804, USA

    Timothy Slattery, Lei Zhao, Mariko Nagashima & John Morser

  4. Clinica Neurologica II, University of Torino, 10126, Torino, Italy

    Antonio Migheli

  5. Department of Medicine, University of Heidelberg, Bergheimen Str. 58, 69115, Heidelberg, Germany

    Peter Nawroth

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Yan, S., Chen, X., Fu, J. et al. RAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease. Nature 382, 685–691 (1996). https://doi.org/10.1038/382685a0

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  • DOI: https://doi.org/10.1038/382685a0

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