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Control of A(beta) release from human neurons by differentiation status and RET signaling

Control of A(beta) release from human neurons by differentiation status and RET signaling

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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. 34(1), pp. 184-199. ISSN 0197-4580. eISSN 1558-1497

@article{Scholz2013-01Contr-20354, title={Control of A(beta) release from human neurons by differentiation status and RET signaling}, year={2013}, doi={10.1016/j.neurobiolaging.2012.03.012}, 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 xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/20354"> <dcterms:title>Control of A(beta) release from human neurons by differentiation status and RET signaling</dcterms:title> <dc:creator>Chernyshova, Yana</dc:creator> <dc:rights>deposit-license</dc:rights> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2012-11-16T07:57:47Z</dc:date> <dc:contributor>Leist, Marcel</dc:contributor> <dc:contributor>Chernyshova, Yana</dc:contributor> <dc:language>eng</dc:language> <dcterms:rights rdf:resource="http://nbn-resolving.org/urn:nbn:de:bsz:352-20140905103605204-4002607-1"/> <dc:contributor>Scholz, Diana</dc:contributor> <dc:creator>Scholz, Diana</dc:creator> <dcterms:issued>2013-01</dcterms:issued> <dcterms:bibliographicCitation>Neurobiology of Aging ; 34 (2013), 1. - S. 184-199</dcterms:bibliographicCitation> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2012-11-16T07:57:47Z</dcterms:available> <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> <dc:creator>Leist, Marcel</dc:creator> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/20354"/> </rdf:Description> </rdf:RDF>

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