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Genetic screen to identify APP metabolism regulators
Abstract   Open access   Peer reviewed

Genetic screen to identify APP metabolism regulators

Aleister Saunders, Preeti Khandelwal, Can Zhang, Jeremy Lee and Daniel R. Marenda
Alzheimer's & dementia, v 4(4S Part 1), pp T29-T29
Jul 2008
DOI: https://doi.org/10.1016/j.jalz.2008.05.063
url
https://doi.org/10.1016/j.jalz.2008.05.063View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

Background Our goal is to identify genes that function to modulate APP processing and Aβ generation. Since genes that increase AD risk are not fully accounted for, and genome scans suggest large genomic regions contain AD positional candidate genes, genes on chromosomes 9 & 10 were screened for their ability to modulate APP metabolism. Methods We used shRNA mediated RNA interference, coupled with an AICD-mediated reporter gene expression assay, in a human neuroblastoma cell lines to silence expression of positional candidate genes and monitor changes in APP metabolism. Results We validated this approach by pharmacologically and genetically targeting the α-, β-, and γ– secretases. We have shown that this screen can identify known regulators of APP metabolism that control proteolysis, intracellular trafficking, maturation and levels of APP and its proteolytic products. Conclusions Here, we identify 25 putative regulators of APP metabolism and characterize them to elucidate their mechanism of action.

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