Year: 2008
Type: article
Abstract: 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. 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. 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. Here, we identify 25 putative regulators of APP metabolism and characterize them to elucidate their mechanism of action.
Source: Alzheimer s & Dementia
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1986474245