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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Peron, Rafaela [1] ; Vatanabe, Izabela Pereira [1] ; Regina Manzine, Patricia [1, 2] ; Camins, Antoni [2, 3, 4] ; Cominetti, Marcia Regina [1]
Total Authors: 5
Affiliation:
[1] Univ Fed Sao Carlos, Dept Gerontol, BR-13565905 Sao Carlos, SP - Brazil
[2] Univ Barcelona, Fac Farm & Ciencies Alimentacio, Dept Farmacol Toxicol & Quim Terapeut, E-08028 Barcelona - Spain
[3] Biomed Res Networking Ctr Neurodegenerat Dis CIBE, Madrid - Spain
[4] Univ Barcelona, Inst Neurociencies, Barcelona 08035 - Spain
Total Affiliations: 4
Document type: Review article
Source: PHARMACEUTICALS; v. 11, n. 1 MAR 2018.
Web of Science Citations: 11
Abstract

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 alpha-secretase that cleaves APP (amyloid precursor protein) in the non-amyloidogenic pathway inhibiting the formation of beta-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, sAPP alpha, which is neuroprotective. As increased ADAM10 activity protects the brain from beta-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. (AU)

FAPESP's process: 16/06226-9 - ADAM10 as a cognitive frailty biomarker
Grantee:Izabela Pereira Vatanabe
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 17/13224-5 - Study of the JNK1 pathway as a selective target for the treatment of cognitive metabolic disorder: ADAM10 protein analysis
Grantee:Patricia Regina Manzine Moralles
Support type: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 15/26084-1 - Evaluation of platelet ADAM10 in non-Alzheimer's dementias
Grantee:Patricia Regina Manzine Moralles
Support type: Scholarships in Brazil - Post-Doctorate