. A presenilin dimer at the core of the gamma-secretase enzyme: insights from parallel analysis of Notch 1 and APP proteolysis. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13075-80. PubMed.

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  1. These are interesting experiments, but I think we have to be careful about interpreting experimetal results like these too literally. To say that cleavages occur at one "side" of a membrane, or in the "middle", so to speak, give the models that we draw of these complex proteins too much credance, at this stage of our understanding of where and how the abeta peptides are generated. No one yet knows how "intramembranous" proteolytic hydrolysis actually occurs, whether it must necessarily happen within the lipid bilayer,and what happens to the "liberated" intramembranous peptides that allow them to escape into the cytosol. (VT Marchesi)

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