Paper
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Wiley JC, Hudson M, Kanning KC, Schecterson LC, Bothwell M. Familial Alzheimer's disease mutations inhibit gamma-secretase-mediated liberation of beta-amyloid precursor protein carboxy-terminal fragment. J Neurochem. 2005 Sep;94(5):1189-201. PubMed.
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Mount Sinai School of Medicine, NYU
FAD mutations inhibit cleavage at the ε site of many PS/γ-secretase substrates. Inhibition at the ε site is predicted to increase cleavage at the γ site, thus increasing Aβ production. This paper offers experimental evidence for this concept.
Picower Institute of MIT
This very interesting article presents data to support the idea that both class II FAD APP mutations and FAD PS1 mutations not only increase levels of Aβ, but also decrease the level of AICD, called CTFγ by the authors. An extremely elegant genetic technique is used to reliably detect this labile fragment. The findings presented in this paper suggest that not only increased Aβ, but also decreased AICD (which normally regulates signaling and transcription) may contribute to the pathology caused by these mutants.
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