. Activation and intrinsic gamma-secretase activity of presenilin 1. Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21435-40. PubMed.


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  1. This is a breakthrough in γ-secretase research. The in vitro reconstitution assay allows us to investigate the function of individual subunits to an extent that is not possible in any other type of assay. The authors show elegantly the proteolytic activity of single presenilin and the activation of presenilin proteolytic activity by PEN-2. The purification method for presenilin is also impressive: It suggests that presenilin can be generated in a preparative scale. Finally, the data suggest that presenilin on its own can be expressed in an active form. It will be much easier to crystallize presenilin alone than in the tetrameric complex.

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