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...
| Authors: | ; ; ; ; |
|---|---|
| Format: | Article |
| Status: | Published version |
| Publication date: | 2018 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/174444 |
| Online Access: | https://hdl.handle.net/2445/174444 |
| Access Level: | Open access |
| Keyword: | Malaltia d'Alzheimer Proteïnes Farmacologia Alzheimer's disease Proteins Pharmacology |
| _version_ | 1878741770168172544 |
|---|---|
| author | Peron, Rafaela |
| author2 | Pereira Vatanabe, Izabela Manzine, Patricia Camins Espuny, Antoni Cominetti, Márcia Regina |
| author2_role | author author author author |
| author_browse | Camins Espuny, Antoni Cominetti, Márcia Regina Manzine, Patricia Pereira Vatanabe, Izabela Peron, Rafaela |
| author_facet | Peron, Rafaela Pereira Vatanabe, Izabela Manzine, Patricia Camins Espuny, Antoni Cominetti, Márcia Regina |
| author_role | author |
| collection | Dipòsit Digital de la UB |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_eb155b7b1fb2c8dafdcb2ae56caa5fe6 |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/174444 |
| publishDate | 2018 |
| publishDateSort | 2018 |
| publisher | MDPI |
| publisherStr | MDPI |
| reponame_str | Dipòsit Digital de la UB |
| spelling | Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer's Disease Treatment Peron, Rafaela Pereira Vatanabe, Izabela Manzine, Patricia Camins Espuny, Antoni Cominetti, Márcia Regina Malaltia d'Alzheimer Proteïnes Farmacologia Alzheimer's disease Proteins Pharmacology 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. MDPI https://hdl.handle.net/2445/174444 |
| spellingShingle | Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer's Disease Treatment Peron, Rafaela Malaltia d'Alzheimer Proteïnes Farmacologia Alzheimer's disease Proteins Pharmacology |
| status_str | publishedVersion |
| title | 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_short | Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer's Disease Treatment |
| title_sort | Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer's Disease Treatment |
| topic | Malaltia d'Alzheimer Proteïnes Farmacologia Alzheimer's disease Proteins Pharmacology |
| topic_facet | Malaltia d'Alzheimer Proteïnes Farmacologia Alzheimer's disease Proteins Pharmacology |
| url | https://hdl.handle.net/2445/174444 |