Bergstrom, P;
Agholme, L;
Nazir, FH;
Satir, TM;
Toombs, J;
Wellington, H;
Strandberg, J;
... Zetterberg, H; + view all
(2016)
Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation.
Scientific Reports
, 6
, Article 292. 10.1038/srep29200.
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Abstract
Amyloid precursor protein (APP) and its cleavage product amyloid β (Aβ) have been thoroughly studied in Alzheimer’s disease. However, APP also appears to be important for neuronal development. Differentiation of induced pluripotent stem cells (iPSCs) towards cortical neurons enables in vitro mechanistic studies on human neuronal development. Here, we investigated expression and proteolytic processing of APP during differentiation of human iPSCs towards cortical neurons over a 100-day period. APP expression remained stable during neuronal differentiation, whereas APP processing changed. α-Cleaved soluble APP (sAPPα) was secreted early during differentiation, from neuronal progenitors, while β-cleaved soluble APP (sAPPβ) was first secreted after deep-layer neurons had formed. Short Aβ peptides, including Aβ1-15/16, peaked during the progenitor stage, while processing shifted towards longer peptides, such as Aβ1-40/42, when post-mitotic neurons appeared. This indicates that APP processing is regulated throughout differentiation of cortical neurons and that amyloidogenic APP processing, as reflected by Aβ1-40/42, is associated with mature neuronal phenotypes.
| Type: | Article |
|---|---|
| Title: | Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/srep29200 |
| Publisher version: | http://dx.doi.org/10.1038/srep29200 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, PLURIPOTENT STEM-CELLS, CEREBRAL-CORTEX DEVELOPMENT, ALZHEIMERS-DISEASE, CEREBROSPINAL-FLUID, SECRETASE CLEAVAGE, IN-VIVO, PEPTIDES, MUTATION, DOMAIN, BACE |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1516258 |
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