Mechanisms involved in amyloid beta production and secretion
2012
University of Konstanz, Konstanz, Germany
Differences in the processing of amyloid precursor protein in young and aged neurons are still not well described and might be important to understand and prevent the onset of Alzheimer's disease. In this study, a human embryonic neuronal precursor cell line is used to study the changes in amyloid precursor protein dynamics along with neuronal maturation and ageing. Differentiated neurons efficiently produced and secreted amyloid-beta, which could be inhibited by cholesterol depletion or secretase inhibition. In aged cells, there was an increase of amyloid-beta secretion without affecting the expression of upstream factors of the amyloidogenic pathway. This phenomenon was associated with GDNF present in the media via the upregulation of RET coreceptor, as other activation mechanisms of the last one were able to produce the same outcome. Inhibitors of protein kinase B completely blocked this effect and the increase of amyloid-beta levels. The results show a mechanism involved in the increased production and secretion of amyloid-beta in aged neurons that could be potentially used to study new therapeutic strategies targeting its up- or downstream regulators.
Control of Aβ release from human neurons by differentiation status and RET signaling
Diana Scholz
Added on: 08-17-2021
[1] https://www.sciencedirect.com/science/article/abs/pii/S0197458012002217[2] https://data.jrc.ec.europa.eu/dataset/a8fd26ef-b113-47ab-92ba-fd2be449c7eb
