Logo do repositório
 
Publicação

α-synuclein interacts with PrPC to induce cognitive impairment through mGluR5 and NMDAR2B

2017Artigo científico Acesso restrito
Ver registo simples
dc.contributor.authorFerreira, Diana
dc.contributor.authorTemido Ferreira, Mariana
dc.contributor.authorVicente Miranda, Hugo
dc.contributor.authorBatalha, Vânia
dc.contributor.authorCoelho, Joana E
dc.contributor.authorSzegö, Éva M
dc.contributor.authorMarques-Morgado, Inês
dc.contributor.authorVaz, Sandra H.
dc.contributor.authorRhee, Jeong Seop
dc.contributor.authorSchmitz, Matthias
dc.contributor.authorZerr, Inga
dc.contributor.authorLopes, Luisa V.
dc.contributor.authorOuteiro, Tiago
dc.date.accessioned2022-12-14T12:35:34Z
dc.date.available2022-12-14T12:35:34Z
dc.date.issued2017
dc.description© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.pt_PT
dc.description.abstractSynucleinopathies, such as Parkinson's disease and dementia with Lewy bodies, are neurodegenerative disorders that are characterized by the accumulation of α-synuclein (aSyn) in intracellular inclusions known as Lewy bodies. Prefibrillar soluble aSyn oligomers, rather than larger inclusions, are currently considered to be crucial species underlying synaptic dysfunction. We identified the cellular prion protein (PrPC) as a key mediator in aSyn-induced synaptic impairment. The aSyn-associated impairment of long-term potentiation was blocked in Prnp null mice and rescued following PrPC blockade. We found that extracellular aSyn oligomers formed a complex with PrPC that induced the phosphorylation of Fyn kinase via metabotropic glutamate receptors 5 (mGluR5). aSyn engagement of PrPC and Fyn activated NMDA receptor (NMDAR) and altered calcium homeostasis. Blockade of mGluR5-evoked phosphorylation of NMDAR in aSyn transgenic mice rescued synaptic and cognitive deficits, supporting the hypothesis that a receptor-mediated mechanism, independent of pore formation and membrane leakage, is sufficient to trigger early synaptic damage induced by extracellular aSyn.pt_PT
dc.description.sponsorshipM.T.F., H.V.M. and J.E.C. were supported by individual grants from Fundação para a Ciência e Tecnologia (FCT) (SFRH/BD/52228/2013; SFRH/BPD/109347/2015; SFRH/BPD/87647/2012); L.V.L. and T.F.O. were supported by a grant from the Fritz Thyssen Stiftung (Az. 10.12.2.165), Germany. L.V.L. received an iMM Lisboa internal fund (BIG – Breakthrough Idea Grant) for part of the project. L.V.L. is an Investigator FCT, Portugal. T.F.O. is supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Germany. LISBOA-01-0145-FEDER-007391, project co-financed by FEDER, POR Lisboa 2020 - Programa Operacional Regional de Lisboa, from PORTUGAL 2020 and by Fundação para a Ciência e a Tecnologia.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNat Neurosci. 2017 Nov;20(11):1569-1579pt_PT
dc.identifier.doi10.1038/nn.4648pt_PT
dc.identifier.eissn1546-1726
dc.identifier.issn1097-6256
dc.identifier.urihttp://hdl.handle.net/10451/55390
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relationSFRH/BD/52228/2013pt_PT
dc.relationTargeting the glycation defenses as a protective strategy for Parkinson’s disease
dc.relationMICROGLIA DYSREGULATION AS TRIGGER FOR CHRONIC NEUROINFLAMMATION: IMPACT FOR AGING AND NEURODEGENERATIVE DISEASES
dc.relation.publisherversionhttps://www.nature.com/neuro/pt_PT
dc.titleα-synuclein interacts with PrPC to induce cognitive impairment through mGluR5 and NMDAR2Bpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberSFRH/BPD/109347/2015
oaire.awardNumberSFRH/BPD/87647/2012
oaire.awardTitleTargeting the glycation defenses as a protective strategy for Parkinson’s disease
oaire.awardTitleMICROGLIA DYSREGULATION AS TRIGGER FOR CHRONIC NEUROINFLAMMATION: IMPACT FOR AGING AND NEURODEGENERATIVE DISEASES
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F109347%2F2015/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F87647%2F2012/PT
oaire.citation.endPage1579pt_PT
oaire.citation.issue11pt_PT
oaire.citation.startPage1569pt_PT
oaire.citation.titleNature Neurosciencept_PT
oaire.citation.volume20pt_PT
person.familyNameFerreira
person.familyNameTemido Ferreira
person.familyNameVicente Miranda
person.familyNameBatalha
person.familyNameCoelho
person.familyNameMarques-Morgado
person.familyNameHenriques Vaz
person.familyNameLopes
person.familyNameOuteiro
person.givenNameDiana
person.givenNameMariana
person.givenNameHugo
person.givenNameVânia
person.givenNameJoana
person.givenNameInês
person.givenNameSandra Cristina
person.givenNameLuisa
person.givenNameTiago
person.identifier30053
person.identifier149432
person.identifier.ciencia-id2719-3B78-B060
person.identifier.ciencia-idA915-3406-B4D3
person.identifier.ciencia-idB310-839B-564D
person.identifier.ciencia-idC31D-A531-95EE
person.identifier.ciencia-id0E1C-952D-61BE
person.identifier.ciencia-id4817-7194-C024
person.identifier.ciencia-idBC14-20AB-8D68
person.identifier.orcid0000-0002-8072-613X
person.identifier.orcid0000-0002-4356-547X
person.identifier.orcid0000-0001-8065-9259
person.identifier.orcid0000-0001-6657-1111
person.identifier.orcid0000-0002-3964-6197
person.identifier.orcid0000-0003-3053-2772
person.identifier.orcid0000-0003-4258-9397
person.identifier.orcid0000-0001-8367-3005
person.identifier.orcid0000-0003-1679-1727
person.identifier.ridI-3525-2013
person.identifier.scopus-author-id57193826021
person.identifier.scopus-author-id7101840699
person.identifier.scopus-author-id7102509159
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication91be058b-f942-429c-8bd7-1c65fd3c85ee
relation.isAuthorOfPublication9bb2081a-0c82-4e7a-9c6e-6c98fdc5a490
relation.isAuthorOfPublicatione5f786d7-df73-4112-8fd6-f3b5944cdb0a
relation.isAuthorOfPublicationb5815f9d-8015-49d7-ba21-f1e3d899b78d
relation.isAuthorOfPublication1301afd3-8056-4d54-983c-0bec935b2d75
relation.isAuthorOfPublication98f0be71-f895-41a6-aa42-038d7902dd3e
relation.isAuthorOfPublicationb282e0fa-69eb-4079-8752-b7dd914f7745
relation.isAuthorOfPublicationdfc15976-b186-45d1-be1c-4592b336edb1
relation.isAuthorOfPublicationaf7b2e31-d9da-4e83-a8f1-702910f80a40
relation.isAuthorOfPublication.latestForDiscovery91be058b-f942-429c-8bd7-1c65fd3c85ee
relation.isProjectOfPublication3b281a18-f52e-4c92-8845-ac3fc91e23ce
relation.isProjectOfPublication77d81cd2-1538-4907-81f6-50e1f1ee1b19
relation.isProjectOfPublication.latestForDiscovery3b281a18-f52e-4c92-8845-ac3fc91e23ce

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura indisponível
Nome:
Synuclein_interacts.pdf
Tamanho:
2.9 MB
Formato:
Adobe Portable Document Format
Ver/Abrir
Licença
A mostrar 1 - 1 de 1
Miniatura indisponível
Nome:
license.txt
Tamanho:
1.2 KB
Formato:
Item-specific license agreed upon to submission
Descrição:
Ver/Abrir

Coleções

IMM - Artigos em Revistas Internacionais
FM - Artigos em Revistas Internacionais