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Insulin receptor in the brain : mechanisms of activation and the role in the CNS pathology and treatment

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dc.contributor.authorPomytkin, Igor
dc.contributor.authorNunes, João
dc.contributor.authorKasatkin, Vladimir
dc.contributor.authorVeniaminova, Ekaterina
dc.contributor.authorDemchenko, Anna
dc.contributor.authorLyundup, Alexey
dc.contributor.authorLesch, Klaus-Peter
dc.contributor.authorPonomarev, Eugene D.
dc.contributor.authorStrekalova, Tatyana
dc.date.accessioned2021-05-28T12:48:43Z
dc.date.available2021-05-28T12:48:43Z
dc.date.issued2018
dc.descriptionCopyright © John Wiley & Sons, Inc. All rights reserved.pt_PT
dc.description.abstractWhile the insulin receptor (IR) was found in the CNS decades ago, the brain was long considered to be an insulin-insensitive organ. This view is currently revisited, given emerging evidence of critical roles of IR-mediated signaling in development, neuroprotection, metabolism, and plasticity in the brain. These diverse cellular and physiological IR activities are distinct from metabolic IR functions in peripheral tissues, thus highlighting region specificity of IR properties. This particularly concerns the fact that two IR isoforms, A and B, are predominantly expressed in either the brain or peripheral tissues, respectively, and neurons express exclusively IR-A. Intriguingly, in comparison with IR-B, IR-A displays high binding affinity and is also activated by low concentrations of insulin-like growth factor-2 (IGF-2), a regulator of neuronal plasticity, whose dysregulation is associated with neuropathologic processes. Deficiencies in IR activation, insulin availability, and downstream IR-related mechanisms may result in aberrant IR-mediated functions and, subsequently, a broad range of brain disorders, including neurodevelopmental syndromes, neoplasms, neurodegenerative conditions, and depression. Here, we discuss findings on the brain-specific features of IR-mediated signaling with focus on mechanisms of primary receptor activation and their roles in the neuropathology. We aimed to uncover the remaining gaps in current knowledge on IR physiology and highlight new therapies targeting IR, such as IR sensitizers.pt_PT
dc.description.sponsorshipThe work reported here was supported by the European Community (EC: the European Union's Seventh Framework Programme (FP7/2007–2013) under Grant No. 602805 (Aggressotype), the Horizon 2020 Research and Innovation Programme under Grant No. 728018 (Eat2beNICE), the “5-100” Russian Academic Excellence Project (to KPL and TS), and the German Research Foundation (DFG: SFB TRR58-A05 to KPL).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCNS Neurosci Ther. 2018 Sep;24(9):763-774pt_PT
dc.identifier.doi10.1111/cns.12866pt_PT
dc.identifier.eissn1755-5949
dc.identifier.issn1755-5930
dc.identifier.urihttp://hdl.handle.net/10451/48233
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherJohn Wiley & Sons, Inc.pt_PT
dc.relationAggression subtyping for improved insight and treatment innovation in psychiatric disorders
dc.relationEffects of Nutrition and Lifestyle on Impulsive, Compulsive, and Externalizing behaviours
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/journal/17555949pt_PT
dc.subjectAlzheimer's diseasept_PT
dc.subjectCentral nervous systempt_PT
dc.subjectInsulin receptorpt_PT
dc.subjectInsulin receptor sensitizerspt_PT
dc.subjectInsulin-like growth factor-2pt_PT
dc.subjectMitochondriapt_PT
dc.titleInsulin receptor in the brain : mechanisms of activation and the role in the CNS pathology and treatmentpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleAggression subtyping for improved insight and treatment innovation in psychiatric disorders
oaire.awardTitleEffects of Nutrition and Lifestyle on Impulsive, Compulsive, and Externalizing behaviours
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/602805/EU
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/728018/EU
oaire.citation.endPage774pt_PT
oaire.citation.issue9pt_PT
oaire.citation.startPage763pt_PT
oaire.citation.titleCNS Neuroscience & Therapeuticspt_PT
oaire.citation.volume24pt_PT
oaire.fundingStreamFP7
oaire.fundingStreamH2020
person.familyNameda Costa Alvares Viegas Nunes
person.givenNameJoão Pedro
person.identifierQ-8648-2017
person.identifier.ciencia-idF413-C6F8-AFF1
person.identifier.orcid0000-0003-0127-5420
person.identifier.scopus-author-id55974674700
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
project.funder.nameEuropean Commission
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication571fa049-46ca-4e54-b555-23993a7e78ca
relation.isAuthorOfPublication.latestForDiscovery571fa049-46ca-4e54-b555-23993a7e78ca
relation.isProjectOfPublication76a52147-6d72-4687-b631-22a7a7b66314
relation.isProjectOfPublicationa0353885-34be-4a96-ad25-63e3b86da03e
relation.isProjectOfPublication.latestForDiscovery76a52147-6d72-4687-b631-22a7a7b66314

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