title: Using Drugs as Molecular Probes: A Computational Chemical Biology Approach in Neurodegenerative Diseases.
abstract: Neurodegenerative diseases including Alzheimer's disease are complex to tackle because of the complexity of the brain, both in structure and function. Such complexity is reflected by the involvement of various brain regions and multiple pathways in the etiology of neurodegenerative diseases that render single drug target approaches ineffective. Particularly in the area of neurodegeneration, attention has been drawn to repurposing existing drugs with proven efficacy and safety profiles. However, there is a lack of systematic analysis of the brain chemical space to predict the feasibility of repurposing strategies. Using a mechanism-based, drug-target interaction modeling approach, we have identified promising drug candidates for repositioning. Mechanistic cause-and-effect models consolidate relevant prior knowledge on drugs, targets, and pathways from the scientific literature and integrate insights derived from experimental data. We demonstrate the power of this approach by predicting two repositioning candidates for Alzheimer's disease and one for amyotrophic lateral sclerosis.
authors.affiliation: Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Sankt Augustin, Germany.|Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn-Aachen International Center for IT, Bonn, Germany.
authors.forename: Mohammad Asif Emran Khan
authors.initials: MA
authors.lastname: Emon
authors.affiliation: Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Sankt Augustin, Germany.|Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn-Aachen International Center for IT, Bonn, Germany.
authors.forename: Alpha Tom
authors.initials: AT
authors.lastname: Kodamullil
authors.affiliation: Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Sankt Augustin, Germany.|Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn-Aachen International Center for IT, Bonn, Germany.
authors.forename: Reagon
authors.initials: R
authors.lastname: Karki
authors.affiliation: Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Sankt Augustin, Germany.
authors.forename: Erfan
authors.initials: E
authors.lastname: Younesi
authors.affiliation: Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Sankt Augustin, Germany.|Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn-Aachen International Center for IT, Bonn, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hofmann-Apitius
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000378:metabolism; D019295:Computational Biology; D003198:Computer Simulation; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use; D000077265:Donepezil; D058492:Drug Repositioning / Q000379:methods; D006801:Humans; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use; D015335:Molecular Probes; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D019782:Riluzole / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D007189:Indans; D015335:Molecular Probes; D018696:Neuroprotective Agents; D010880:Piperidines; D019782:Riluzole; D016572:Cyclosporine; D000077265:Donepezil
keywords: Alzheimer disease; amyotrophic lateral sclerosis; biological expression 
  language; disease-drug modeling; drug repositioning; neurodegenerative diseases