Title: γ-secretase heterogeneity in the Aph1 subunit: relevance for Alzheimer’s Disease
Authors: Serneels, Lutgarde *
Van Biervliet, Jerome *
Craessaerts, Kathleen
Dejaegere, Tim
Horré, Katrien
Vanhoutvin, Tine
Esselmann, H.
Paul, S.
Schäfer, M.K.
Berezovska, O.
Hyman, B.T.
Sprangers, B.
Sciot, Raphael
Moons, Lieve
Jucker, M.
Yang, Z.
May, P.C.
Karran, E.
Willtfang, J.
D'Hooge, Rudi
De Strooper, Bart # ×
Issue Date: 1-May-2009
Publisher: American Association for the Advancement of Science
Series Title: Science vol:324 issue:5927 pages:639-642
Abstract: The gamma-secretase complex plays a role in Alzheimer's disease and cancer progression. The development of clinically useful inhibitors, however, is complicated by the role of the gamma-secretase complex in regulated intramembrane proteolysis of Notch and other essential proteins. Different gamma-secretase complexes containing different Presenilin or Aph1 protein subunits are present in various tissues. Here we show that these complexes have heterogeneous biochemical and physiological properties. Specific inactivation of the Aph1B gamma-secretase in a mouse Alzheimer's disease model led to improvements of Alzheimer's disease-relevant phenotypic features without any Notch-related side effects. The Aph1B complex contributes to total gamma-secretase activity in the human brain, and thus specific targeting of Aph1B-containing gamma-secretase complexes may help generate less toxic therapies for Alzheimer's disease.
Description: Single sentence summary: Aph1B γ-secretase has a distinct conformation, and genetic ablation improves Alzheimer’s disease phenotypes without affecting Notch signaling in the mouse
ISSN: 0036-8075
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Biological Psychology
Laboratory for the Research of Neurodegenerative Diseases
Translational Cell & Tissue Research
Department of Human Genetics - miscellaneous
Molecular Genetics Section (-)
Animal Physiology and Neurobiology Section - miscellaneous
* (joint) first author
× corresponding author
# (joint) last author

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