Publikation: Control of A(beta) release from human neurons by differentiation status and RET signaling
Dateien
Datum
Autor:innen
Herausgeber:innen
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
URI (zitierfähiger Link)
DOI (zitierfähiger Link)
Internationale Patentnummer
Link zur Lizenz
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Sammlungen
Core Facility der Universität Konstanz
Titel in einer weiteren Sprache
Publikationstyp
Publikationsstatus
Erschienen in
Zusammenfassung
Few studies have compared the processing of endogenous human amyloid precursor protein (APP) in younger and older neurons. Here, we characterized LUHMES cells as a human model to study Alzheimer’s disease-related processes during neuronal maturation and aging. Differentiated LUHMES expressed and spontaneously processed APP via the secretase pathways, and they secreted amyloid (beta) (A(beta) ) peptide. This was inhibited by cholesterol depletion or secretase inhibition, but not by block of tau phosphorylation. In vitro aged cells increased A (beta) secretion without upregulation of APP or secretases. We identified the medium constituent glial cell line-derived neurotrophic factor (GDNF) as responsible for this effect. GDNF-triggered A (beta) release was associated with rapid upregulation of the GDNF coreceptor "rearranged during transfection" (RET). Other direct (neurturin) or indirect (nerve growth factor) RET activators also increased A(beta) , whereas different neurotrophins were ineffective. Downstream of RET, we found activation of protein kinase B (AKT) to be involved. Accordingly, inhibitors of the AKT regulator phosphatidylinositol-3-kinase completely blocked GDNF-triggered AKT phosphorylation and A (beta) increase. This suggests that RET signaling affects A(beta) release from aging neurons.
Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
Schlagwörter
Konferenz
Rezension
Zitieren
ISO 690
SCHOLZ, Diana, Yana CHERNYSHOVA, Marcel LEIST, 2013. Control of A(beta) release from human neurons by differentiation status and RET signaling. In: Neurobiology of Aging. 2013, 34(1), pp. 184-199. ISSN 0197-4580. eISSN 1558-1497. Available under: doi: 10.1016/j.neurobiolaging.2012.03.012BibTex
@article{Scholz2013-01Contr-20354,
year={2013},
doi={10.1016/j.neurobiolaging.2012.03.012},
title={Control of A(beta) release from human neurons by differentiation status and RET signaling},
number={1},
volume={34},
issn={0197-4580},
journal={Neurobiology of Aging},
pages={184--199},
author={Scholz, Diana and Chernyshova, Yana and Leist, Marcel}
}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/123456789/20354">
<bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/20354"/>
<dc:language>eng</dc:language>
<dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
<dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2012-11-16T07:57:47Z</dcterms:available>
<dc:creator>Scholz, Diana</dc:creator>
<dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/20354/2/Scholz_203540.pdf"/>
<dcterms:issued>2013-01</dcterms:issued>
<dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/20354/2/Scholz_203540.pdf"/>
<dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/>
<foaf:homepage rdf:resource="http://localhost:8080/"/>
<dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2012-11-16T07:57:47Z</dc:date>
<dc:creator>Chernyshova, Yana</dc:creator>
<dc:rights>terms-of-use</dc:rights>
<dc:creator>Leist, Marcel</dc:creator>
<dc:contributor>Leist, Marcel</dc:contributor>
<void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
<dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
<dcterms:title>Control of A(beta) release from human neurons by differentiation status and RET signaling</dcterms:title>
<dc:contributor>Scholz, Diana</dc:contributor>
<dcterms:abstract xml:lang="eng">Few studies have compared the processing of endogenous human amyloid precursor protein (APP) in younger and older neurons. Here, we characterized LUHMES cells as a human model to study Alzheimer’s disease-related processes during neuronal maturation and aging. Differentiated LUHMES expressed and spontaneously processed APP via the secretase pathways, and they secreted amyloid (beta) (A(beta) ) peptide. This was inhibited by cholesterol depletion or secretase inhibition, but not by block of tau phosphorylation. In vitro aged cells increased A (beta) secretion without upregulation of APP or secretases. We identified the medium constituent glial cell line-derived neurotrophic factor (GDNF) as responsible for this effect. GDNF-triggered A (beta) release was associated with rapid upregulation of the GDNF coreceptor "rearranged during transfection" (RET). Other direct (neurturin) or indirect (nerve growth factor) RET activators also increased A(beta) , whereas different neurotrophins were ineffective. Downstream of RET, we found activation of protein kinase B (AKT) to be involved. Accordingly, inhibitors of the AKT regulator phosphatidylinositol-3-kinase completely blocked GDNF-triggered AKT phosphorylation and A (beta) increase. This suggests that RET signaling affects A(beta) release from aging neurons.</dcterms:abstract>
<dcterms:bibliographicCitation>Neurobiology of Aging ; 34 (2013), 1. - S. 184-199</dcterms:bibliographicCitation>
<dc:contributor>Chernyshova, Yana</dc:contributor>
</rdf:Description>
</rdf:RDF>
