Paper
- Milestone
- Alzforum Recommends
Kimberly WT, LaVoie MJ, Ostaszewski BL, Ye W, Wolfe MS, Selkoe DJ. Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2. Proc Natl Acad Sci U S A. 2003 May 27;100(11):6382-7. PubMed.
Recommends
Please login to recommend the paper.
Comments
AstraZeneca
This is an extremely important paper that, along with recent publications from Iwatsubo et al., 2003 and Haass et al., 2003, finally show that the γ-sceretase complex is composed of four transmembrane proteins: presenillin, nicastrin, Aph-1 and Pen-2. It is a clear and convincing study that builds on previous work from the same group and brings together genetic and biochemical evidence for the structure, function and composition of the γ-sceretase complex in a human cell model system. Kimberly et al. show that these four components are required for the maturation and stability of the complex, and the production of amyloid-β. The challenge now remains to elucidate regulatory mechanisms and substrate-specificity of the complex and to biochemically reconstitute the components in an in-vitro system in order to rationally design inhibitory compounds.
References:
Takasugi N, Tomita T, Hayashi I, Tsuruoka M, Niimura M, Takahashi Y, Thinakaran G, Iwatsubo T. The role of presenilin cofactors in the gamma-secretase complex. Nature. 2003 Mar 27;422(6930):438-41. PubMed.
Edbauer D, Winkler E, Regula JT, Pesold B, Steiner H, Haass C. Reconstitution of gamma-secretase activity. Nat Cell Biol. 2003 May;5(5):486-8. PubMed.
Make a Comment
To make a comment you must login or register.