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Substrate check of γ-secretase

Nature Structural & Molecular Biology volume 17, pages 140–141 (2010)Cite this article

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γ-secretase cleaves multiple substrates with essential roles from development to neurodegeneration, and its aberrant processing underlies human disorders including Alzheimer's disease (AD). Tian et al. now identify a domain in the β-amyloid precursor protein (APP) that inhibits γ-secretase activity and show that certain familial AD–linked APP mutations within this domain impair this inhibition, resulting in increased β-amyloid generation. The study thus reveals a novel mechanism whereby γ-secretase's activity is influenced by its own substrate.

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Figure 1: Model for negative regulation of γ-secretase.

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Authors and Affiliations

  1. Yun-wu Zhang and Huaxi Xu are at the Institute for Biomedical Research and the Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Xiamen University, Xiamen, China, and the Neurodegenerative Disease Research Program, Burnham Institute for Medical Research, La Jolla, California, USA.,

    Yun-wu Zhang & Huaxi Xu

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  1. Yun-wu Zhang
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  2. Huaxi Xu
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Correspondence to Huaxi Xu.

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Zhang, Yw., Xu, H. Substrate check of γ-secretase. Nat Struct Mol Biol 17, 140–141 (2010). https://doi.org/10.1038/nsmb0210-140

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