Human genome-guided identification of memory-modulating drugs

Lade...
Vorschaubild
Dateien
Papassotiropoulos_261951.pdf
Papassotiropoulos_261951.pdfGröße: 796.04 KBDownloads: 278
Datum
2013
Autor:innen
Papassotiropoulos, Andreas
Gerhards, Christiane
Heck, Angela
Ackermann, Sandra
Aerni, Amanda
Schicktanz, Nathalie
Auschra, Bianca
Demougin, Philippe
Mumme, Eva
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
DOI (zitierfähiger Link)
ArXiv-ID
Internationale Patentnummer
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Open Access Green
Sammlungen
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Proceedings of the National Academy of Sciences of the United States of America. 2013, 110(46), pp. E4369-E4374. ISSN 0027-8424. eISSN 1091-6490
Zusammenfassung

In the last decade there has been an exponential increase in knowledge about the genetic basis of complex human traits, including neuropsychiatric disorders. It is not clear, however, to what extent this knowledge can be used as a starting point for drug identification, one of the central hopes of the human genome project. The aim of the present study was to identify memory-modulating compounds through the use of human genetic information. We performed a multinational collaborative study, which included assessment of aversive memory—a trait central to posttraumatic stress disorder—and a gene-set analysis in healthy individuals. We identified 20 potential drug target genes in two genomewide-corrected gene sets: the neuroactive ligand–receptor interaction and the long-term depression gene set. In a subsequent double-blind, placebo-controlled study in healthy volunteers, we aimed at providing a proof of concept for the genome-guided identification of memory modulating compounds. Pharmacological intervention at the neuroactive ligand–receptor interaction gene set led to significant reduction of aversive memory. The findings demonstrate that genome information, along with appropriate data mining methodology, can be used as a starting point for the identification of memory-modulating compounds.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
150 Psychologie
Schlagwörter
emotional memory, pharmacology, PTSD
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690PAPASSOTIROPOULOS, Andreas, Christiane GERHARDS, Angela HECK, Sandra ACKERMANN, Amanda AERNI, Nathalie SCHICKTANZ, Bianca AUSCHRA, Philippe DEMOUGIN, Eva MUMME, Thomas ELBERT, Verena ERTL, Leo GSCHWIND, Edveena HANSER, Kim-Dung HUYNH, Frank JESSEN, Iris-Tatjana KOLASSA, Annette MILNIK, Paolo PAGANETTI, Klara SPALEK, Christian VOGLER, Andreas MUHS, Andrea PFEIFER, Dominique J.-F. DE QUERVAIN, 2013. Human genome-guided identification of memory-modulating drugs. In: Proceedings of the National Academy of Sciences of the United States of America. 2013, 110(46), pp. E4369-E4374. ISSN 0027-8424. eISSN 1091-6490
BibTex
@article{Papassotiropoulos2013Human-26195,
  year={2013},
  title={Human genome-guided identification of memory-modulating drugs},
  url={http://dx.doi.org/    10.1073/pnas.1314478110},
  number={46},
  volume={110},
  issn={0027-8424},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  pages={E4369--E4374},
  author={Papassotiropoulos, Andreas and Gerhards, Christiane and Heck, Angela and Ackermann, Sandra and Aerni, Amanda and Schicktanz, Nathalie and Auschra, Bianca and Demougin, Philippe and Mumme, Eva and Elbert, Thomas and Ertl, Verena and Gschwind, Leo and Hanser, Edveena and Huynh, Kim-Dung and Jessen, Frank and Kolassa, Iris-Tatjana and Milnik, Annette and Paganetti, Paolo and Spalek, Klara and Vogler, Christian and Muhs, Andreas and Pfeifer, Andrea and de Quervain, Dominique J.-F.}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/26195">
    <dc:contributor>Vogler, Christian</dc:contributor>
    <dc:contributor>Gerhards, Christiane</dc:contributor>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/43"/>
    <dcterms:abstract xml:lang="eng">In the last decade there has been an exponential increase in knowledge about the genetic basis of complex human traits, including neuropsychiatric disorders. It is not clear, however, to what extent this knowledge can be used as a starting point for drug identification, one of the central hopes of the human genome project. The aim of the present study was to identify memory-modulating compounds through the use of human genetic information. We performed a multinational collaborative study, which included assessment of aversive memory—a trait central to posttraumatic stress disorder—and a gene-set analysis in healthy individuals. We identified 20 potential drug target genes in two genomewide-corrected gene sets: the neuroactive ligand–receptor interaction and the long-term depression gene set. In a subsequent double-blind, placebo-controlled study in healthy volunteers, we aimed at providing a proof of concept for the genome-guided identification of memory modulating compounds. Pharmacological intervention at the neuroactive ligand–receptor interaction gene set led to significant reduction of aversive memory. The findings demonstrate that genome information, along with appropriate data mining methodology, can be used as a starting point for the identification of memory-modulating compounds.</dcterms:abstract>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2014-02-11T10:45:39Z</dc:date>
    <dc:creator>Mumme, Eva</dc:creator>
    <dc:creator>Elbert, Thomas</dc:creator>
    <dc:creator>Ackermann, Sandra</dc:creator>
    <dc:creator>Gschwind, Leo</dc:creator>
    <dc:creator>Huynh, Kim-Dung</dc:creator>
    <dc:contributor>Gschwind, Leo</dc:contributor>
    <dc:contributor>Ackermann, Sandra</dc:contributor>
    <dc:contributor>Jessen, Frank</dc:contributor>
    <dc:contributor>Huynh, Kim-Dung</dc:contributor>
    <dc:contributor>Mumme, Eva</dc:contributor>
    <dc:contributor>Schicktanz, Nathalie</dc:contributor>
    <dc:creator>Heck, Angela</dc:creator>
    <dc:contributor>de Quervain, Dominique J.-F.</dc:contributor>
    <dc:contributor>Ertl, Verena</dc:contributor>
    <dc:creator>Ertl, Verena</dc:creator>
    <dc:creator>Kolassa, Iris-Tatjana</dc:creator>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dcterms:issued>2013</dcterms:issued>
    <dc:creator>Spalek, Klara</dc:creator>
    <dc:creator>Papassotiropoulos, Andreas</dc:creator>
    <dc:contributor>Hanser, Edveena</dc:contributor>
    <dc:contributor>Papassotiropoulos, Andreas</dc:contributor>
    <dc:creator>Paganetti, Paolo</dc:creator>
    <dcterms:bibliographicCitation>Proceedings of the National Academy of Sciences of the United States of America ; 110 (2013), 46. - E4369–E4374</dcterms:bibliographicCitation>
    <dc:creator>Jessen, Frank</dc:creator>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/26195/2/Papassotiropoulos_261951.pdf"/>
    <dc:rights>terms-of-use</dc:rights>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/43"/>
    <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/26195"/>
    <dc:creator>Vogler, Christian</dc:creator>
    <dc:creator>Schicktanz, Nathalie</dc:creator>
    <dc:creator>Muhs, Andreas</dc:creator>
    <dc:contributor>Paganetti, Paolo</dc:contributor>
    <dc:contributor>Heck, Angela</dc:contributor>
    <dc:creator>Aerni, Amanda</dc:creator>
    <dc:creator>Pfeifer, Andrea</dc:creator>
    <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/>
    <dc:creator>Gerhards, Christiane</dc:creator>
    <dc:language>eng</dc:language>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:creator>Hanser, Edveena</dc:creator>
    <dc:contributor>Muhs, Andreas</dc:contributor>
    <dc:contributor>Milnik, Annette</dc:contributor>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/26195/2/Papassotiropoulos_261951.pdf"/>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2014-02-11T10:45:39Z</dcterms:available>
    <dcterms:title>Human genome-guided identification of memory-modulating drugs</dcterms:title>
    <dc:creator>de Quervain, Dominique J.-F.</dc:creator>
    <dc:contributor>Elbert, Thomas</dc:contributor>
    <dc:contributor>Spalek, Klara</dc:contributor>
    <dc:contributor>Demougin, Philippe</dc:contributor>
    <dc:creator>Milnik, Annette</dc:creator>
    <dc:contributor>Pfeifer, Andrea</dc:contributor>
    <dc:creator>Demougin, Philippe</dc:creator>
    <dc:contributor>Auschra, Bianca</dc:contributor>
    <dc:contributor>Kolassa, Iris-Tatjana</dc:contributor>
    <dc:contributor>Aerni, Amanda</dc:contributor>
    <dc:creator>Auschra, Bianca</dc:creator>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
Prüfdatum der URL
Prüfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Diese Publikation teilen