An integrative genome-wide transcriptome reveals that candesartan is neuroprotective and a candidate therapeutic for Alzheimer's disease

Alzheimer's Research & Therapy
Abdel G ElkahlounJuan M Saavedra

Abstract

Alzheimer's disease is the most frequent age-related dementia, and is currently without treatment. To identify possible targets for early therapeutic intervention we focused on glutamate excitotoxicity, a major early pathogenic factor, and the effects of candesartan, an angiotensin receptor blocker of neuroprotective efficacy in cell cultures and rodent models of Alzheimer's disease. The overall goal of the study was to determine whether gene analysis of drug effects in a primary neuronal culture correlate with alterations in gene expression in Alzheimer's disease, thus providing further preclinical evidence of beneficial therapeutic effects. Primary neuronal cultures were treated with candesartan at neuroprotective concentrations followed by excitotoxic glutamate amounts. We performed genome-wide expression profile analysis and data evaluation by ingenuity pathway analysis and gene set enrichment analysis, compared with alterations in gene expression from two independent published datasets identified by microarray analysis of postmortem hippocampus from Alzheimer's disease patients. Preferential expression in cerebrovascular endothelial cells or neurons was analyzed by comparison to published gene expression in these cells iso...Continue Reading

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Citations

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Datasets Mentioned

BETA
GSE67036
GSEA
GSE36980
GSE46871
GSE48350
GSE12293
GSE12679
and
GSE1297

Methods Mentioned

BETA
laser capture microdissection
chips
Chip
laser-capture microdissection
laser

Software Mentioned

GSEA
Gene Chip Operating
GSEA gene set enrichment analysis
ingenuity pathway analysis ( IPA )
Partek Genomics Suite
gene set enrichment analysis ( GSEA )
Partek Genomics Suites
GraphPad
IPA
GraphPad Prism

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