γ-Secretase Heterogeneity in the Aph1 Subunit: Relevance for Alzheimer’s Disease-Reference-Cited by-同舟云学术

γ-Secretase Heterogeneity in the Aph1 Subunit: Relevance for Alzheimer’s Disease

Published:2009-05 Issue:5927 Volume:324 Page:639-642
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Serneels Lutgarde¹²,Van Biervliet Jérôme¹²,Craessaerts Katleen¹²,Dejaegere Tim¹²,Horré Katrien¹²,Van Houtvin Tine¹²,Esselmann Hermann³⁴,Paul Sabine³⁴,Schäfer Martin K.⁵,Berezovska Oksana⁶,Hyman Bradley T.⁶,Sprangers Ben⁷,Sciot Raf⁸,Moons Lieve⁹,Jucker Mathias¹⁰,Yang Zhixiang¹¹,May Patrick C.¹¹,Karran Eric¹²,Wiltfang Jens³⁴,D’Hooge Rudi¹³,De Strooper Bart¹²

Affiliation:

1. Department for Molecular and Developmental Genetics, VIB, KULeuven, Herestraat 49, 3000 Leuven, Belgium.

2. Center for Human Genetics, KULeuven, Herestraat 49, 3000 Leuven, Belgium.

3. Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.

4. Department of Psychiatry and Psychotherapy, Rhine State Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany.

5. Department of Molecular Neurosciences, Institute of Anatomy and Cell Biology, Philipps University, D-35032 Marburg, Germany.

6. Harvard Medical School, Massachusetts General Hospital, MassGeneral Institute for Neurodegenerative Disorders, Charlestown, MA 02129, USA.

7. Laboratory of Experimental Transplantation, KULeuven, 3000 Leuven, Belgium.

8. Laboratory of Morphology and Molecular Pathology, KULeuven, 3000 Leuven, Belgium.

9. Laboratory of Neural Circuit Development and Regeneration, Department of Biology, KULeuven, 3000 Leuven, Belgium.

10. Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany.

11. Neuroscience Discovery Research, Lilly Research Labs, Eli Lilly and Co., Indianapolis, IN 46285, USA.

12. Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK.

13. Laboratory of Biological Psychology, Department of Psychology, KULeuven, 3000 Leuven, Belgium.

Abstract

Tactical Target Intramembrane proteolysis by the γ-secretase complex is important during development and in the pathology of Alzheimer's disease. γ-Secretase has usually been considered as a homogeneous activity. Serneels et al. (p. 639 , published online 19 March; see the Perspective by Golde and Kukar ) now show that the Aph1B component of the γ-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 γ-secretase more generally.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference24 articles.

1. Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein

2. Aph-1, Pen-2, and Nicastrin with Presenilin Generate an Active γ-Secretase Complex

3. Coordinated and widespread expression of γ-secretase in vivo: evidence for size and molecular heterogeneity

4. Identification of Distinct γ-Secretase Complexes with Different APH-1 Variants

5. Differential contribution of the three Aph1 genes to -secretase activity in vivo

Cited by 229 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Long-Term, Sex-Specific Effects of GCRsim and Gamma Irradiation on the Brains, Hearts, and Kidneys of Mice with Alzheimer’s Disease Mutations;International Journal of Molecular Sciences;2024-08-16

2. Monoclonal antibodies and aptamers: The future therapeutics for Alzheimer's disease;Acta Pharmaceutica Sinica B;2024-07

3. TGR5 deficiency in excitatory neurons ameliorates Alzheimer’s pathology by regulating APP processing;Science Advances;2024-06-28

4. Apo and Aβ46-bound γ-secretase structures provide insights into amyloid-β processing by the APH-1B isoform;Nature Communications;2024-05-27

5. Alzheimer’s disease-related presenilins are key to intestinal epithelial cell function and gut immune homoeostasis;Gut;2024-04-29