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Home: Papers of the Week
Annotation


Deng Y, Tarassishin L, Kallhoff V, Peethumnongsin E, Wu L, Li YM, Zheng H. Deletion of presenilin 1 hydrophilic loop sequence leads to impaired gamma-secretase activity and exacerbated amyloid pathology. J Neurosci. 2006 Apr 5;26(14):3845-54. PubMed Abstract

Comments on Paper and Primary News
  Comment by:  Nikolaos K. Robakis
Submitted 15 April 2006  |  Permalink Posted 18 April 2006
  I recommend this paper

This is a very interesting paper. It indicates that loss of PS1 function may lead to plaque pathology and amyloid depositions. The authors conclude that it is the loss of the γ-secretase function of PS1 and the reduction of Aβ1-40 that lead to increased plaque pathology. Although this conclusion is in agreement with several reports in the last years that presenilin FAD mutations cause a loss (rather than a gain) of γ-secretase function, it is not necessary that the mechanism of plaque pathology in AD involves directly the γ-secretase function. Increased plaque pathology (and even Aβ production) may also result from increased activities in apoptotic pathways that, in turn, may be caused by many factors including a loss of PS1 function in cell survival pathways, a γ-secretase-independent function of PS1 (Baki et al., 2004).

View all comments by Nikolaos K. Robakis

  Comment by:  Tommaso Russo, ARF Advisor
Submitted 18 April 2006  |  Permalink Posted 18 April 2006
  I recommend this paper

  Comment by:  Bart De Strooper, ARF Advisor
Submitted 24 April 2006  |  Permalink Posted 25 April 2006
  I recommend this paper
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REAGENTS/MATERIAL:

The following antibodies were used in this study: PS1N and PS1C polyclonal antibodies were raised against PS1 N-terminal peptide (1–15 amino acids) and C-terminal peptide (455–467 amino acids), respectively, and APPC was raised against the last 15 amino acids of the human APP sequence. Mouse anti-PS1 loop monoclonal antibody was purchased from Chemicon (Temecula, CA). Anti-nicastrin antibody was raised against 688–708 amino acids of the protein and was available from Affinity BioReagents (Golden, CO). Anti-Aph1 and anti-Pen2 antibodies were from Zymed (San Francisco, CA), anti-b-catenin, anti-N-cadherin, and anti-glycogen synthase kinase 3b (GSK3b) were purchased from BD Transduction Laboratories (Lexington, KY), anti-cyclin-dependent kinase 5 (Cdk5) (C-8) was from Santa Cruz Biotechnology (Santa Cruz, CA), and 6E10 monoclonal antibody was obtained from Signet Laboratories (Dedham, MA).

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