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Caspase activation without apoptosis: insight into Aβ initiation of neurodegeneration

Nature Neuroscience volume 14, pages 5–6 (2011)Cite this article

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New work in a mouse model of Alzheimer's disease suggests that early-stage synaptic and memory impairments are caused by abnormal activation of a protease and a phosphatase, both of which could be targeted by inhibitory drugs.

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Figure 1: Soluble Aβ leads to elevation of intracellular calcium13 and caspase activation1 that in turn both activate calcineurin, a critical mediator of both long-term depression phenomenon and spine loss, causing deafferentation and likely additional pro-apoptotic stimulation.

References

  1. D'Amelio, M. et al. Nat. Neurosci. 14, 69–76 (2011).

    Article  CAS  Google Scholar 

  2. Irizarry, M.C., McNamara, M., Fedorchak, K., Hsiao, K. & Hyman, B.T. J. Neuropathol. Exp. Neurol. 56, 965–973 (1997).

    Article  CAS  Google Scholar 

  3. Li, Z. et al. Cell 141, 859–871 (2010).

    Article  CAS  Google Scholar 

  4. Su, J.H., Zhao, M., Anderson, A.J., Srinivasan, A. & Cotman, C.W. Brain Res. 898, 350–357 (2001).

    Article  CAS  Google Scholar 

  5. Louneva, N. et al. Am. J. Pathol. 173, 1488–1495 (2008).

    Article  CAS  Google Scholar 

  6. Ribe, E.M., Serrano-Saiz, E., Akpan, N. & Troy, C.M. Biochem. J. 415, 165–182 (2008).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  8. de Calignon, A., Spires-Jones, T.L., Pitstick, R., Carlson, G.A. & Hyman, B.T. J. Neuropathol. Exp. Neurol. 68, 757–761 (2009).

    Article  CAS  Google Scholar 

  9. Kamenetz, F. et al. Neuron 37, 925–937 (2003).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  11. Snyder, E.M. et al. Nat. Neurosci. 8, 1051–1058 (2005).

    Article  CAS  Google Scholar 

  12. Wu, H.Y. et al. J. Neurosci. 30, 2636–2649 (2010).

    Article  CAS  Google Scholar 

  13. Kuchibhotla, K.V. et al. Neuron 59, 214–225 (2008).

    Article  CAS  Google Scholar 

  14. Dineley, K.T. et al. J. Neurosci. Res. 88, 2923–2932 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Koffie, R.M. et al. Proc. Natl. Acad. Sci. USA 106, 4012–4017 (2009).

    Article  CAS  Google Scholar 

Download references

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  1. The author is in the Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.,

    Bradley T Hyman

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  1. Bradley T Hyman
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Correspondence to Bradley T Hyman.

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The author declares no competing financial interests.

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Hyman, B. Caspase activation without apoptosis: insight into Aβ initiation of neurodegeneration. Nat Neurosci 14, 5–6 (2011). https://doi.org/10.1038/nn0111-5

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