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Identification of regulators of APP metabolism on chromosome 10
Journal article   Open access   Peer reviewed

Identification of regulators of APP metabolism on chromosome 10

Preeti Khandelwal, Jennifer Schuster, Nathan Fried, Travis D'Cruz, Jeremy Lee and Aleister Saunders
Alzheimer's & dementia, v 4(4S Part 11), pp T363-T363
Jul 2008
DOI: https://doi.org/10.1016/j.jalz.2008.05.1074
url
https://doi.org/10.1016/j.jalz.2008.05.1074View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  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 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 16 putative regulators of APP metabolism and characterize them to elucidate their mechanism of action.

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