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Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury

Nature Medicine volume 15, pages 377–379 (2009)Cite this article

Abstract

Amyloid-β (Aβ) peptides, found in Alzheimer's disease brain, accumulate rapidly after traumatic brain injury (TBI) in both humans and animals. Here we show that blocking either β- or γ-secretase, enzymes required for production of Aβ from amyloid precursor protein (APP), can ameliorate motor and cognitive deficits and reduce cell loss after experimental TBI in mice. Thus, APP secretases are promising targets for treatment of TBI.

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Figure 1: Bace1 ablation protects against TBI-induced cell loss and behavioral deficits in vivo.
Figure 2: Chronic γ-secretase inhibition protects against TBI-induced cell loss and behavioral deficits in vivo.

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Acknowledgements

We would like to thank A. Pajoohesh-Ganji and P. Washington for technical assistance; S. Fricke and O. Rodriguez of the Small Animal Imaging Laboratory at Georgetown University; and P. Mathews (Nathan S. Kline Institute) for antibody C1/6.1. This work was funded by grant R03NS57635 (M.P.B.) and a pilot award from the National Capital Area Rehabilitation Research Network R24HD050845 (M.P.B.), both from the US National Institutes of Health, and by the Klingel Family Foundation (M.P.B.).

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Authors and Affiliations

  1. Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA

    David J Loane, Ana Pocivavsek, Charbel E-H Moussa, Rachel Thompson, Alan I Faden, G William Rebeck & Mark P Burns

  2. Department of Neurology, Georgetown University Medical Center, Washington, DC, USA

    Yasuji Matsuoka

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  1. David J Loane
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Correspondence to Mark P Burns.

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Supplementary Figs. 1 and 2 and Supplementary Methods (PDF 672 kb)

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Loane, D., Pocivavsek, A., Moussa, CH. et al. Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury. Nat Med 15, 377–379 (2009). https://doi.org/10.1038/nm.1940

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