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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.
 View all comments by Mark Farmery |
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 I recommend this paper
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