Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer's Disease Treatment

ADAM (a disintegrin and metalloproteinase) is a family of widely expressed, transmembrane and secreted proteins of approximately 750 amino acids in length with functions in cell adhesion and proteolytic processing of the ectodomains of diverse cell-surface receptors and signaling molecules. ADAM10 i...

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Autores: Peron, Rafaela, Pereira Vatanabe, Izabela, Manzine, Patricia, Camins Espuny, Antoni, Cominetti, Márcia Regina
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/174444
Acceso en línea:https://hdl.handle.net/2445/174444
Access Level:acceso abierto
Palabra clave:Malaltia d'Alzheimer
Proteïnes
Farmacologia
Alzheimer's disease
Proteins
Pharmacology
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spelling Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer's Disease TreatmentPeron, RafaelaPereira Vatanabe, IzabelaManzine, PatriciaCamins Espuny, AntoniCominetti, Márcia ReginaMalaltia d'AlzheimerProteïnesFarmacologiaAlzheimer's diseaseProteinsPharmacologyADAM (a disintegrin and metalloproteinase) is a family of widely expressed, transmembrane and secreted proteins of approximately 750 amino acids in length with functions in cell adhesion and proteolytic processing of the ectodomains of diverse cell-surface receptors and signaling molecules. ADAM10 is the main α-secretase that cleaves APP (amyloid precursor protein) in the non-amyloidogenic pathway inhibiting the formation of β-amyloid peptide, whose accumulation and aggregation leads to neuronal degeneration in Alzheimer's disease (AD). ADAM10 is a membrane-anchored metalloprotease that sheds, besides APP, the ectodomain of a large variety of cell-surface proteins including cytokines, adhesion molecules and notch. APP cleavage by ADAM10 results in the production of an APP-derived fragment, sAPPα, which is neuroprotective. As increased ADAM10 activity protects the brain from β-amyloid deposition in AD, this strategy has been proved to be effective in treating neurodegenerative diseases, including AD. Here, we describe the physiological mechanisms regulating ADAM10 expression at different levels, aiming to propose strategies for AD treatment. We report in this review on the physiological regulation of ADAM10 at the transcriptional level, by epigenetic factors, miRNAs and/or translational and post-translational levels. In addition, we describe the conditions that can change ADAM10 expression in vitro and in vivo, and discuss how this knowledge may help in AD treatment. Regulation of ADAM10 is achieved by multiple mechanisms that include transcriptional, translational and post-translational strategies, which we will summarize in this review.MDPI2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/174444Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3390/ph11010012Pharmaceuticals, 2018, vol. 11, num. 1, p. E12https://doi.org/10.3390/ph11010012cc-by (c) Peron, Rafaela et al., 2018http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1744442026-05-27T06:46:51Z
dc.title.none.fl_str_mv Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer's Disease Treatment
title Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer's Disease Treatment
spellingShingle Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer's Disease Treatment
Peron, Rafaela
Malaltia d'Alzheimer
Proteïnes
Farmacologia
Alzheimer's disease
Proteins
Pharmacology
title_short Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer's Disease Treatment
title_full Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer's Disease Treatment
title_fullStr Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer's Disease Treatment
title_full_unstemmed Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer's Disease Treatment
title_sort Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer's Disease Treatment
dc.creator.none.fl_str_mv Peron, Rafaela
Pereira Vatanabe, Izabela
Manzine, Patricia
Camins Espuny, Antoni
Cominetti, Márcia Regina
author Peron, Rafaela
author_facet Peron, Rafaela
Pereira Vatanabe, Izabela
Manzine, Patricia
Camins Espuny, Antoni
Cominetti, Márcia Regina
author_role author
author2 Pereira Vatanabe, Izabela
Manzine, Patricia
Camins Espuny, Antoni
Cominetti, Márcia Regina
author2_role author
author
author
author
dc.subject.none.fl_str_mv Malaltia d'Alzheimer
Proteïnes
Farmacologia
Alzheimer's disease
Proteins
Pharmacology
topic Malaltia d'Alzheimer
Proteïnes
Farmacologia
Alzheimer's disease
Proteins
Pharmacology
description ADAM (a disintegrin and metalloproteinase) is a family of widely expressed, transmembrane and secreted proteins of approximately 750 amino acids in length with functions in cell adhesion and proteolytic processing of the ectodomains of diverse cell-surface receptors and signaling molecules. ADAM10 is the main α-secretase that cleaves APP (amyloid precursor protein) in the non-amyloidogenic pathway inhibiting the formation of β-amyloid peptide, whose accumulation and aggregation leads to neuronal degeneration in Alzheimer's disease (AD). ADAM10 is a membrane-anchored metalloprotease that sheds, besides APP, the ectodomain of a large variety of cell-surface proteins including cytokines, adhesion molecules and notch. APP cleavage by ADAM10 results in the production of an APP-derived fragment, sAPPα, which is neuroprotective. As increased ADAM10 activity protects the brain from β-amyloid deposition in AD, this strategy has been proved to be effective in treating neurodegenerative diseases, including AD. Here, we describe the physiological mechanisms regulating ADAM10 expression at different levels, aiming to propose strategies for AD treatment. We report in this review on the physiological regulation of ADAM10 at the transcriptional level, by epigenetic factors, miRNAs and/or translational and post-translational levels. In addition, we describe the conditions that can change ADAM10 expression in vitro and in vivo, and discuss how this knowledge may help in AD treatment. Regulation of ADAM10 is achieved by multiple mechanisms that include transcriptional, translational and post-translational strategies, which we will summarize in this review.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/174444
url https://hdl.handle.net/2445/174444
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/ph11010012
Pharmaceuticals, 2018, vol. 11, num. 1, p. E12
https://doi.org/10.3390/ph11010012
dc.rights.none.fl_str_mv cc-by (c) Peron, Rafaela et al., 2018
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Peron, Rafaela et al., 2018
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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