Type of Publication: | Journal article |
URI (citable link): | http://nbn-resolving.de/urn:nbn:de:bsz:352-203540 |
Author: | Scholz, Diana; Chernyshova, Yana; Leist, Marcel |
Year of publication: | 2013 |
Published in: | Neurobiology of Aging ; 34 (2013), 1. - pp. 184-199. - ISSN 0197-4580. - eISSN 1558-1497 |
Pubmed ID: | 22534065 |
DOI (citable link): | https://dx.doi.org/10.1016/j.neurobiolaging.2012.03.012 |
Summary: |
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.
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Subject (DDC): | 570 Biosciences, Biology |
Keywords: | LUHMES, Alzheimer’s disease, A (beta), RET, GDNF |
Link to License: | In Copyright |
Bibliography of Konstanz: | Yes |
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. Available under: doi: 10.1016/j.neurobiolaging.2012.03.012
@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} }
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