Begum, Sadia;
De Alvarez, Javier Andres;
Manzoni, Claudia;
Arber, Charlie;
Lewis, Patrick A;
(2026)
In Silico Phosphoproteomic Analysis Reveals Divergent Regulation of Presenilin 1 and Presenilin 2.
NeuroMolecular Medicine
, 28
(1)
, Article 5. 10.1007/s12017-026-08906-z.
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Abstract
The Presenilins are multi-pass transmembrane proteins that form part of the multi-protein gamma secretase complex. The hydrolytic activity of the gamma secretase complex is responsible for the cleavage of a wide range of substrates, including the amyloid precursor protein (APP) - a proteolytic event that is the final step in the production of the amyloid beta peptide, a protein fragment deposited in the brains of individuals with Alzheimer's disease (AD). Both PSEN1 and PSEN2, the genes encoding the Presenilins, are mutated in familial AD, generating intense interest in the activity and function of these proteins. Despite this attention, the post-translational modification and regulation of the Presenilins is poorly understood. In order to address this gap in our knowledge, a bioinformatic approach was taken to examine the extant evidence for Presenilin phosphorylation. Derived from the Phosphosite repository, these data reveal divergent patterns of phosphorylation across Presenilin 1 and 2, highlighting distinct regulatory pathways that have implications for our understanding of the biology of these proteins, gamma secretase, and drug discovery targeting this complex.
| Type: | Article |
|---|---|
| Title: | In Silico Phosphoproteomic Analysis Reveals Divergent Regulation of Presenilin 1 and Presenilin 2 |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s12017-026-08906-z |
| Publisher version: | https://doi.org/10.1007/s12017-026-08906-z |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Alzheimer’s disease, Gamma secretase, Presenilin, Signal transduction, Presenilin-1, Presenilin-2, Humans, Phosphorylation, Proteomics, Protein Processing, Post-Translational, Alzheimer Disease, Computer Simulation, Amyloid Precursor Protein Secretases, Computational Biology |
| 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 Life 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 Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10221056 |
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