Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/104001
DC Field | Value | Language |
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dc.contributor.author | Sousa, Luís | - |
dc.contributor.author | Guarda, Mariana | - |
dc.contributor.author | Meneses, Maria João | - |
dc.contributor.author | Macedo, M. Paula | - |
dc.contributor.author | Vicente Miranda, Hugo | - |
dc.date.accessioned | 2022-12-15T10:36:55Z | - |
dc.date.available | 2022-12-15T10:36:55Z | - |
dc.date.issued | 2021-12 | - |
dc.identifier.issn | 0022-3417 | pt |
dc.identifier.issn | 1096-9896 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/104001 | - |
dc.description.abstract | Insulin-degrading enzyme (IDE) function goes far beyond its known proteolytic role as a regulator of insulin levels. IDE has a wide substrate promiscuity, degrading several proteins such as amyloid-β peptide, glucagon, islet amyloid polypeptide (IAPP), and insulin-like growth factors, which have diverse physiological and pathophysiological functions. Importantly, IDE plays other non-proteolytic functions such as: a chaperone/dead-end chaperone, an E1-ubiquitin activating enzyme, and a proteasome modulator. It also responds as a heat shock protein, regulating cellular proteostasis. Notably, amyloidogenic proteins such as IAPP, amyloid-β, and α-synuclein have been reported as substrates for IDE chaperone activity. This is of utmost importance as failure of IDE may result in increased protein aggregation, a key hallmark in the pathogenesis of beta cells in type 2 diabetes mellitus and of neurons in neurodegenerative diseases such as Alzheimer's and Parkinson's disease. In this review, we focus on the biochemical and biophysical properties of IDE and the regulation of its physiological functions. We further raise the hypothesis that IDE plays a central role in the pathological context of dysmetabolic and neurodegenerative diseases and discuss its potential as a therapeutic target. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. | pt |
dc.language.iso | por | pt |
dc.relation | UID/Multi/04462/2013 | pt |
dc.relation | PTDC/BIM-MET/2115/2014 | pt |
dc.relation | PTDC/MEC-MET/29314/2017 | pt |
dc.relation | mtFOIE GRAS (734719) | pt |
dc.relation | SFRH/BD/144743/2019 | pt |
dc.rights | embargoedAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | pt |
dc.subject | amyloid-β; insulin; insulin-degrading enzyme; neurodegenerative disorders; therapeutics; type 2 diabetes mellitus; α-synuclein | pt |
dc.subject.mesh | Animals | pt |
dc.subject.mesh | Humans | pt |
dc.subject.mesh | Insulysin | pt |
dc.subject.mesh | Metabolic Diseases | pt |
dc.subject.mesh | Neurodegenerative Diseases | pt |
dc.title | Insulin-degrading enzyme: an ally against metabolic and neurodegenerative diseases | pt |
dc.type | article | - |
degois.publication.firstPage | 346 | pt |
degois.publication.lastPage | 361 | pt |
degois.publication.issue | 4 | pt |
dc.relation.publisherversion | https://onlinelibrary.wiley.com/doi/10.1002/path.5777 | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1002/path.5777 | pt |
degois.publication.volume | 255 | pt |
dc.date.embargo | 2022-12-01 | * |
uc.date.periodoEmbargo | 365 | pt |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | pt | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | Com Texto completo | - |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
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IDE paper.pdf | 5.04 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License