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Activation of microglial cells by β-amyloid protein and interferon-γ

Abstract

ALZHEIMER'S disease is the most common cause of progressive intellectual failure1. The lesions that develop, called senile plaques, are extracellular deposits principally composed of insoluble aggregates of β-amyloid protein (Aβ), infiltrated by reactive microglia and astrocytes2,3. Although Aβ, and a portion of it, the fragment 25–35 (Aβ(25–35)), have been shown to exert a direct toxic effect on neurons4–6, the role of microglia in such neuronal injury remains unclear7. Here we report a synergistic effect between Aβ and interferon-γ (IFN-γ) in triggering the production of reactive nitrogen intermediates and tumour-necrosis factor-α (TNF-α) from microglia. Furthermore, using co-culture experiments, we show that activation of microglia with IFN-γ and Aβ leads to neuronal cell injury in vitro. These findings suggest that Aβ and IFN-γ activate microglia to produce reactive nitrogen intermediates and TNF-α, and this may have a role in the pathogenesis of neuronal degeneration observed in ageing and Alzheimer's disease.

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References

  1. Selkoe, D. J., Bell, D. S., Podlisny, M. B., Price, D. L. & Cork, L. C. Science 235, 873–877 (1987).

    Article  ADS  CAS  Google Scholar 

  2. Yankner, B. A. & Mesulam, M. M. New Engl. J. Med. 325, 1849–1857 (1991).

    Article  CAS  Google Scholar 

  3. Mullan, M. & Crawford, F. Trends Neurosci. 16, 398–403 (1993).

    Article  CAS  Google Scholar 

  4. Yankner, B. A., Duffy, L. K. & Kirschner, D. A. Science 250, 279–282 (1990).

    Article  ADS  CAS  Google Scholar 

  5. Kowall, N. W., Beal, M. F., Busciglio, J., Duffy, L. K. & Yankner, B. A. Proc. natn. Acad. Sci. U.S.A. 88, 7247–7251 (1991).

    Article  ADS  CAS  Google Scholar 

  6. Pike, C. J., Burdick, D., Walencewicz, A. J., Glabe, C. G. & Cotman, C. W. J. Neurosci. 13, 1676–1687 (1993).

    Article  CAS  Google Scholar 

  7. Perry, V. H., Andersson, P. B. & Gordon, S. Trends Neurosci. 16, 268–273 (1993).

    Article  CAS  Google Scholar 

  8. Corradin, S. B., Manuel, J., Donini, S. D., Quattrocchi, E. & Ricciardi-Castagnoli, P. Glia 7, 255–262 (1993).

    Article  CAS  Google Scholar 

  9. Simmons, L. K. et al. Molec. Pharmacol. 45, 373–379 (1994).

    CAS  Google Scholar 

  10. Oswald, I. P., Wynn, T. A., Sher, A. & James, S. L. Proc. natn. Acad. Sci. U.S.A. 89, 8676–8680 (1992).

    Article  ADS  CAS  Google Scholar 

  11. Chao, C. C., Hu, S., Molitor, T. W., Shaskan, E. G. & Peterson, P. K. J. Immun. 149, 2736–2741 (1992).

    CAS  PubMed  Google Scholar 

  12. Chao, C. C., Molitor, T. W. & Hu, S. J. Immun. 151, 1473–1481 (1993).

    CAS  PubMed  Google Scholar 

  13. Boje, K. M. & Arora, P. K. Brain Res. 587, 250–256 (1992).

    Article  CAS  Google Scholar 

  14. Olanow, C. W. Trends Neurosci. 16, 439–444 (1993).

    Article  CAS  Google Scholar 

  15. Coyle, J. T. & Puttfarcken, P. Science 262, 689–692 (1993).

    Article  ADS  CAS  Google Scholar 

  16. Hensley, K. et al. Proc. natn. Acad. Sci. U.S.A. 91, 3270–3273 (1994).

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  18. Aranjuo, D. M. & Cotman, C. W. Brain Res. 569, 141–145 (1992).

    Article  Google Scholar 

  19. Dickson, D. W., Mattiace, L. A. & Yen, S. H. (abstr.) Soc. Neurosci. 16, 1267 (1990).

    Google Scholar 

  20. Cheng, B., Christakos, S. & Mattson, M. P. Neuron 12, 139–153 (1994).

    Article  CAS  Google Scholar 

  21. Agresti, C., Aloisi, F. & Levi, G. Devl Biol. 144, 16–29 (1991).

    Article  CAS  Google Scholar 

  22. Ding, A. H., Nathan, C. F. & Stuehr, D. J. J. Immun. 141, 2407–2412 (1988).

    CAS  Google Scholar 

  23. Otvos, L., Szendrei, G. I., Lee, V. M. Y. & Mantsch, H. H. Eur. J. Biochem. 211, 249–257 (1993).

    Article  CAS  Google Scholar 

  24. Cassatella, M. A., Meda, L., Bonora, S., Ceska, M. & Constantin, G. J. exp. Med. 178, 2207–2211 (1993).

    Article  CAS  Google Scholar 

  25. Hernandez-Caselles, T. & Stutman, O. J. Immun. 151, 3999–4012 (1993).

    CAS  PubMed  Google Scholar 

  26. Villalba, M. et al. J. biol. Chem. 269, 2468–2476 (1994).

    CAS  PubMed  Google Scholar 

  27. Sher, P. K. & Hu, S. Brain Res. Bull. 25, 697–701 (1990).

    Article  CAS  Google Scholar 

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Meda, L., Cassatella, M., Szendrei, G. et al. Activation of microglial cells by β-amyloid protein and interferon-γ. Nature 374, 647–650 (1995). https://doi.org/10.1038/374647a0

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