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Presenilin 1 Modulates Acetylcholinesterase Trafficking and Maturation

In Alzheimer’s disease (AD), the reduction in acetylcholinesterase (AChE) enzymatic activity is not paralleled with changes in its protein levels, suggesting the presence of a considerable enzymatically inactive pool in the brain. In the present study, we validated previous findings, and, since inac...

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Autores principales: Cortés-Gómez, María-Ángeles, Barberá, Víctor M., Alom, Jordi, Sáez-Valero, Javier, García-Ayllón, María-Salud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864477/
https://www.ncbi.nlm.nih.gov/pubmed/36674948
http://dx.doi.org/10.3390/ijms24021437
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author Cortés-Gómez, María-Ángeles
Barberá, Víctor M.
Alom, Jordi
Sáez-Valero, Javier
García-Ayllón, María-Salud
author_facet Cortés-Gómez, María-Ángeles
Barberá, Víctor M.
Alom, Jordi
Sáez-Valero, Javier
García-Ayllón, María-Salud
author_sort Cortés-Gómez, María-Ángeles
collection PubMed
description In Alzheimer’s disease (AD), the reduction in acetylcholinesterase (AChE) enzymatic activity is not paralleled with changes in its protein levels, suggesting the presence of a considerable enzymatically inactive pool in the brain. In the present study, we validated previous findings, and, since inactive forms could result from post-translational modifications, we analyzed the glycosylation of AChE by lectin binding in brain samples from sporadic and familial AD (sAD and fAD). Most of the enzymatically active AChE was bound to lectins Canavalia ensiformis (Con A) and Lens culinaris agglutinin (LCA) that recognize terminal mannoses, whereas Western blot assays showed a very low percentage of AChE protein being recognized by the lectin. This indicates that active and inactive forms of AChE vary in their glycosylation pattern, particularly in the presence of terminal mannoses in active ones. Moreover, sAD subjects showed reduced binding to terminal mannoses compared to non-demented controls, while, for fAD patients that carry mutations in the PSEN1 gene, the binding was higher. The role of presenilin-1 (PS1) in modulating AChE glycosylation was then studied in a cellular model that overexpresses PS1 (CHO-PS1). In CHO-PS1 cells, binding to LCA indicates that AChE displays more terminal mannoses in oligosaccharides with a fucosylated core. Immunocytochemical assays also demonstrated increased presence of AChE in the trans-Golgi. Moreover, AChE enzymatic activity was higher in plasmatic membrane of CHO-PS1 cells. Thus, our results indicate that PS1 modulates trafficking and maturation of AChE in Golgi regions favoring the presence of active forms in the membrane.
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spelling pubmed-98644772023-01-22 Presenilin 1 Modulates Acetylcholinesterase Trafficking and Maturation Cortés-Gómez, María-Ángeles Barberá, Víctor M. Alom, Jordi Sáez-Valero, Javier García-Ayllón, María-Salud Int J Mol Sci Article In Alzheimer’s disease (AD), the reduction in acetylcholinesterase (AChE) enzymatic activity is not paralleled with changes in its protein levels, suggesting the presence of a considerable enzymatically inactive pool in the brain. In the present study, we validated previous findings, and, since inactive forms could result from post-translational modifications, we analyzed the glycosylation of AChE by lectin binding in brain samples from sporadic and familial AD (sAD and fAD). Most of the enzymatically active AChE was bound to lectins Canavalia ensiformis (Con A) and Lens culinaris agglutinin (LCA) that recognize terminal mannoses, whereas Western blot assays showed a very low percentage of AChE protein being recognized by the lectin. This indicates that active and inactive forms of AChE vary in their glycosylation pattern, particularly in the presence of terminal mannoses in active ones. Moreover, sAD subjects showed reduced binding to terminal mannoses compared to non-demented controls, while, for fAD patients that carry mutations in the PSEN1 gene, the binding was higher. The role of presenilin-1 (PS1) in modulating AChE glycosylation was then studied in a cellular model that overexpresses PS1 (CHO-PS1). In CHO-PS1 cells, binding to LCA indicates that AChE displays more terminal mannoses in oligosaccharides with a fucosylated core. Immunocytochemical assays also demonstrated increased presence of AChE in the trans-Golgi. Moreover, AChE enzymatic activity was higher in plasmatic membrane of CHO-PS1 cells. Thus, our results indicate that PS1 modulates trafficking and maturation of AChE in Golgi regions favoring the presence of active forms in the membrane. MDPI 2023-01-11 /pmc/articles/PMC9864477/ /pubmed/36674948 http://dx.doi.org/10.3390/ijms24021437 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cortés-Gómez, María-Ángeles
Barberá, Víctor M.
Alom, Jordi
Sáez-Valero, Javier
García-Ayllón, María-Salud
Presenilin 1 Modulates Acetylcholinesterase Trafficking and Maturation
title Presenilin 1 Modulates Acetylcholinesterase Trafficking and Maturation
title_full Presenilin 1 Modulates Acetylcholinesterase Trafficking and Maturation
title_fullStr Presenilin 1 Modulates Acetylcholinesterase Trafficking and Maturation
title_full_unstemmed Presenilin 1 Modulates Acetylcholinesterase Trafficking and Maturation
title_short Presenilin 1 Modulates Acetylcholinesterase Trafficking and Maturation
title_sort presenilin 1 modulates acetylcholinesterase trafficking and maturation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864477/
https://www.ncbi.nlm.nih.gov/pubmed/36674948
http://dx.doi.org/10.3390/ijms24021437
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