title: Bioinformatics methods in drug repurposing for Alzheimer's disease.
abstract: Alarming epidemiological features of Alzheimer's disease impose curative treatment rather than symptomatic relief. Drug repurposing, that is reappraisal of a substance's indications against other diseases, offers time, cost and efficiency benefits in drug development, especially when in silico techniques are used. In this study, we have used gene signatures, where up- and down-regulated gene lists summarize a cell's gene expression perturbation from a drug or disease. To cope with the inherent biological and computational noise, we used an integrative approach on five disease-related microarray data sets of hippocampal origin with three different methods of evaluating differential gene expression and four drug repurposing tools. We found a list of 27 potential anti-Alzheimer agents that were additionally processed with regard to molecular similarity, pathway/ontology enrichment and network analysis. Protein kinase C, histone deacetylase, glycogen synthase kinase 3 and arginase inhibitors appear consistently in the resultant drug list and may exert their pharmacologic action in an epidermal growth factor receptor-mediated subpathway of Alzheimer's disease.
authors.forename: John C
authors.initials: JC
authors.lastname: Siavelis
authors.forename: Marilena M
authors.initials: MM
authors.lastname: Bourdakou
authors.forename: Emmanouil I
authors.initials: EI
authors.lastname: Athanasiadis
authors.forename: George M
authors.initials: GM
authors.lastname: Spyrou
authors.forename: Konstantina S
authors.initials: KS
authors.lastname: Nikita
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D058492:Drug Repositioning / Q000379:methods*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D025941:Protein Interaction Mapping / Q000379:methods
chemical_list: D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents
keywords: Alzheimer’s disease; Connectivity Map; drug repurposing; epidermal growth factor receptor pathway; gene signatures