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Down-regulation of the ATP-binding cassette transporter 2 (Abca2) reduces amyloid-β production by altering Nicastrin maturation and intracellular localization.

Authors: Michaki, Vasiliki  Guix, Francesc X  Vennekens, Krist'l  Munck, Sebastian  Dingwall, Colin  Davis, John B  Townsend, Danyelle M  Tew, Kenneth D  Feiguin, Fabian  De Strooper, Bart  Dotti, Carlos G  Wahle, Tina 
Citation: Michaki V, etal., J Biol Chem. 2012 Jan 6;287(2):1100-11. doi: 10.1074/jbc.M111.288258. Epub 2011 Nov 15.
Pubmed: (View Article at PubMed) PMID:22086926
DOI: Full-text: DOI:10.1074/jbc.M111.288258

Clinical, pharmacological, biochemical, and genetic evidence support the notion that alteration of cholesterol homeostasis strongly predisposes to Alzheimer 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 Aβ generation, without affecting Notch cleavage.

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CRRD Object Information
CRRD ID: 14697726
Created: 2019-08-03
Species: All species
Last Modified: 2019-08-03
Status: ACTIVE



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