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Sci. Signal., 5 May 2009
Vol. 2, Issue 69, p. ec158
[DOI: 10.1126/scisignal.269ec158]


Alzheimer's Disease Tactical Target

Stella M. Hurtley

Science, AAAS, Cambridge CB2 1LQ, UK

Intramembrane proteolysis by the {gamma}-secretase complex is important during development and in the pathology of Alzheimer’s disease. {gamma}-Secretase has usually been considered as a homogeneous activity. Serneels et al. (see the Perspective by Golde and Kukar) now show that the Aph1B component of the {gamma}-secretase complex is responsible for the generation of long β-amyloid species involved in Alzheimer's disease. In a mouse model of Alzheimer’s disease, full knockout of Aph1B improved disease phenotypes, without the sort of toxicity previously observed when targeting {gamma}-secretase more generally.

L. Serneels, J. Van Biervliet, K. Craessaerts, T. Dejaegere, K. Horré, T. Van Houtvin, H. Esselmann, S. Paul, M. K. Schäfer, O. Berezovska, B. T. Hyman, B. Sprangers, R. Sciot, L. Moons, M. Jucker, Z. Yang, P. C. May, E. Karran, J. Wiltfang, R. D’Hooge, B. De Strooper, {gamma}-Secretase heterogeneity in the Aph1 subunit: Relevance for Alzheimer’s disease. Science 324, 639–642 (2009). [Abstract] [Full Text]

T. E. Golde, T. L. Kukar, Avoiding unintended toxicity. Science 324, 603–604 (2009). [Summary] [Full Text]

Citation: S. M. Hurtley, Tactical Target. Sci. Signal. 2, ec158 (2009).

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