| First Author | Michaki V | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 2 | Pages | 1100-11 |
| PubMed ID | 22086926 | Mgi Jnum | J:277862 |
| Mgi Id | MGI:6355606 | Doi | 10.1074/jbc.M111.288258 |
| Citation | Michaki V, et al. (2012) Down-regulation of the ATP-binding cassette transporter 2 (Abca2) reduces amyloid-beta production by altering Nicastrin maturation and intracellular localization. J Biol Chem 287(2):1100-11 |
| abstractText | 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-beta (Abeta) generation. In vitro studies revealed altered gamma-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 gamma-secretase processing of APP, and thus Abeta generation, without affecting Notch cleavage. |
