Llorente, Patricia;
Martins, Soraia;
Sastre, Isabel;
Aldudo, Jesús;
Recuero, María;
Adjaye, James;
Bullido, Maria J;
(2020)
Matrix Metalloproteinase 14 Mediates APP Proteolysis and Lysosomal Alterations Induced by Oxidative Stress in Human Neuronal Cells.
Oxidative Medicine and Cellular Longevity
, 2020
, Article 5917187. 10.1155/2020/5917187.
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Abstract
The alteration of amyloid precursor protein (APP) proteolysis is a hallmark of Alzheimer’s disease (AD). Recent studies have described noncanonical pathways of APP processing that seem partly executed by lysosomal enzymes. Our laboratory’s in vitro human SK-N-MC model has shown that oxidative stress (OS) alters the lysosomal degradation pathway and the processing/metabolism of APP. The present study identifies the lysosomal protein matrix metalloproteinase 14 (MMP14) as a protease involved in the APP noncanonical processing. Previous expression analyses of the above cells showed MMP14 to be overexpressed under OS. In the present work, its role in changes in OS-induced APP proteolysis and lysosomal load was examined. The results show that MMP14 mediates the accumulation of an ≈85 kDa N-terminal APP fragment and increases the lysosome load induced by OS. These results were validated in neurons and neural progenitor cells generated from the induced pluripotent stem cells of patients with sporadic AD, reinforcing the idea that MMP14 may offer a therapeutic target in this disease.
| Type: | Article |
|---|---|
| Title: | Matrix Metalloproteinase 14 Mediates APP Proteolysis and Lysosomal Alterations Induced by Oxidative Stress in Human Neuronal Cells |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1155/2020/5917187 |
| Publisher version: | https://doi.org/10.1155/2020/5917187 |
| Language: | English |
| Additional information: | © 2020 Patricia Llorente et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited |
| Keywords: | Alzheimer Disease, Amyloid Precursor Protein Secretases, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Humans, Lysosomes, Matrix Metalloproteinase 14, Neurons, Oxidative Stress, Proteolysis |
| 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 Population Health Sciences > UCL EGA Institute for Womens Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10179355 |
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