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Retinal pigment epithelium degeneration caused by aggregation of PRPF31 and the role of HSP70 family of proteins

2019-12-31Journal article Open access
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dc.contributor.authorValdés-Sánchez, Lourdes
dc.contributor.authorCalado, Sofia
dc.contributor.authorde la Cerda, Berta
dc.contributor.authorAramburu, Ana
dc.contributor.authorGarcía-Delgado, Ana B
dc.contributor.authorMassalini, Simone
dc.contributor.authorMontero-Sánchez, Adoración
dc.contributor.authorBhatia, Vaibhav
dc.contributor.authorRodríguez-Bocanegra, Eduardo
dc.contributor.authorDiez-Lloret, Andrea
dc.contributor.authorRodríguez-Martínez, Daniel
dc.contributor.authorChakarova, Christina
dc.contributor.authorBhattacharya, Shom S
dc.contributor.authorDíaz-Corrales, Francisco J
dc.date.accessioned2020-01-06T15:10:35Z
dc.date.available2020-01-06T15:10:35Z
dc.date.issued2019-12-31
dc.date.updated2020-01-01T04:35:13Z
dc.description.abstractBackground Mutations in pre-mRNA splicing factor PRPF31 can lead to retinitis pigmentosa (RP). Although the exact disease mechanism remains unknown, it has been hypothesized that haploinsufficiency might be involved in the pathophysiology of the disease. Methods In this study, we have analyzed a mouse model containing the p.A216P mutation in Prpf31 gene. Results We found that mutant Prpf31 protein produces cytoplasmic aggregates in the retinal pigment epithelium and decreasing the protein levels of this splicing factor in the nucleus. Additionally, normal protein was recruited in insoluble aggregates when the mutant protein was overexpressed in vitro. In response to protein aggregation, Hspa4l is overexpressed. This member of the HSP70 family of chaperones might contribute to the correct folding and solubilization of the mutant protein, allowing its translocation to the nucleus. Conclusions Our data suggests that a mechanism haploinsufficiency and dominant-negative is involved in retinal degeneration due to mutations in PRPF31. HSP70 over-expression might be a new therapeutic target for the treatment of retinal degeneration due to PRPF31 mutations.pt_PT
dc.description.sponsorshipThis project has been financed through a) The ISCIII (Miguel Servet-I, 2015), co-financed by the European Regional Development Fund (ERDF), No CP15/00071. b) The European Union’s Horizon 2020 research and innovation program, under grant agreement No 634479. c) Regional Ministry of Economy, Innovation and Science of the Junta de Andalucía, No P09-CTS-04967.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMolecular Medicine. 2019 Dec 31;26(1):1pt_PT
dc.identifier.dois10020-019-0124-zpt_PT
dc.identifier.urihttp://hdl.handle.net/10400.1/13403
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherBMCpt_PT
dc.relationExploring the combined role of genetic and non-genetic factors for developing Age-Related Macular Degeneration: A systems level analysis of disease subgroups, risk factors, and pathways
dc.rights.holderThe Author(s)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleRetinal pigment epithelium degeneration caused by aggregation of PRPF31 and the role of HSP70 family of proteinspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleExploring the combined role of genetic and non-genetic factors for developing Age-Related Macular Degeneration: A systems level analysis of disease subgroups, risk factors, and pathways
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/634479/EU
oaire.citation.issue1pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleMolecular Medicinept_PT
oaire.citation.volume26pt_PT
oaire.fundingStreamH2020
person.familyNameCalado
person.givenNameSofia
person.identifier.ciencia-id7C1A-91BA-B6A0
person.identifier.orcid0000-0001-5509-4145
person.identifier.ridK-2202-2016
person.identifier.scopus-author-id56426215600
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication950f7df3-f549-497f-9ace-8edd58a83e08
relation.isAuthorOfPublication.latestForDiscovery950f7df3-f549-497f-9ace-8edd58a83e08
relation.isProjectOfPublication1b4deecb-bf4b-43d5-a99a-479d5ac51834
relation.isProjectOfPublication.latestForDiscovery1b4deecb-bf4b-43d5-a99a-479d5ac51834

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