Title: Downregulation of the ATP-binding cassette transporter 2 (Abca2) reduces Amyloid-β production by altering Nicastrin maturation and intracellular localization
Authors: Michaki, Vasiliki
Guix, Francesc
Vennekens, Kristel
Munck, Sebastian
Dingwall, Colin
Davis, John B
Townsend, Danyelle M
Tew, Kenneth D
Feguin, Fabian
De Strooper, Bart
Dotti, Carlos
Wahle, Tina # ×
Issue Date: 2012
Publisher: American Society for Biochemistry and Molecular Biology
Series Title: Journal of Biological Chemistry vol:287 issue:2 pages:1100-1111
Abstract: Clinical, pharmacological, biochemical and genetic evidences support the notion that alteration of cholesterol homeostasis strongly predisposes to Alzheimers disease (AD). The ATP-binding-cassette-transporter-2 (Abca2), which plays a role in intracellular sterol trafficking, has been genetically linked to AD. It is unclear how these two processes are related. Here we demonstrate that down-regulation of Abca2 in mammalian cells leads to decreased Amyloid-β (Aβ) generation. In vitro studies revealed altered γ-secretase complex formation in Abca2 knock out cells due to the altered levels, post-translational modification and subcellular localization of Nicastrin. Reduced Abca2 levels in mammalian cells in vitro, in Drosophila melanogaster and in mice resulted in altered γ-secretase processing of APP, and thus the generation of Aβ, without affecting Notch cleavage.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory for the Research of Neurodegenerative Diseases
Laboratory of Neuronal Differentiation
× corresponding author
# (joint) last author

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