. Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury. Nat Med. 2009 Apr;15(4):377-9. PubMed.

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  1. This paper is on how blocking Aβ production may help treat traumatic brain injury. With respect to β-secretase, this was studied using BACE1 knockout mice, but with respect to γ- secretase, an inhibitor (DAPT) was used. The results look promising and suggest another important use for γ-secretase inhibitors. In this case, since chronic treatment may not be necessary, the Notch issue may not be so important (i.e., global inhibitors may be okay without the need for a Notch-selective modulator).

  2. I recommend the primary paper.

    View all comments by J. Lucy Boyd
  3. The report from Loane et al. raises several intriguing questions:

    1. What are the mechanisms underlying the effects of DAPT treatment and BACE knockout in the setting of TBI?

    2. Can administration of APP secretase inhibitors starting at clinically realizable times after TBI be effective at improving cognitive and behavioral effects of injury?

    3. What pharmacodynamic assays for the most relevant effects of such secretase inhibitors should be used in preclinical and clinical studies?

    Hopefully, this report will stimulate further work on the important topic of the relationship between TBI and AD.

    View all comments by David Brody