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Home: Papers of the Week
Annotation


Schroeter EH, Ilagan MX, Brunkan AL, Hecimovic S, Li YM, Xu M, Lewis HD, Saxena MT, De Strooper B, Coonrod A, Tomita T, Iwatsubo T, Moore CL, Goate A, Wolfe MS, Shearman M, Kopan R. 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 Abstract, View on AlzSWAN

  
Comments on Paper and Primary News
  Primary News: Presenilin—Two Heads Better Than One?

Comment by:  Vincent Marchesi, ARF Advisor
Submitted 21 October 2003  |  Permalink Posted 21 October 2003

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)

View all comments by Vincent Marchesi

  Comment by:  Andre Delacourte, ARF Advisor
Submitted 30 October 2003  |  Permalink Posted 30 October 2003
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REAGENTS/MATERIAL:

Immunoprecipitation used Myc epitope anti-a-Myc 9E10 antibody. Ab40 levels were determined by ELISA (BioSource International).

In Western blot assays Notch was detected with monoclonal 9E10 a-Myc antibody. 9N14 is a polyclonal antibody raised against a peptide antigen composed of residues 1–14 of human PS1. Other antibodies against PS1 are: anti-PS1 (NT1) (monoclonal, gift of P. Mathews), 13A11 (monoclonal, provided by P. Seubert, Elan Pharmaceuticals), and R22 (polyclonal).

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