miR-335 targets LRRK2 and mitigates inflammation in Parkinson’s disease

Detalhes bibliográficos
Autor(a) principal: Oliveira, Sara
Data de Publicação: 2021
Outros Autores: Dionísio, Pedro A., Gaspar, Maria Manuela, Correia Guedes, Leonor, Coelho, Miguel, Rosa, Mário Miguel, Ferreira, Joaquim J, Amaral, Joana D., Rodrigues, Cecília M. P.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/49651
Resumo: Copyright © 2021 Oliveira, Dionísio, Gaspar, Correia Guedes, Coelho, Rosa, Ferreira, Amaral and Rodrigues. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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spelling miR-335 targets LRRK2 and mitigates inflammation in Parkinson’s diseaseLRRK2Parkinson’s diseaseInflammationmiR-335NecroptosisCopyright © 2021 Oliveira, Dionísio, Gaspar, Correia Guedes, Coelho, Rosa, Ferreira, Amaral and Rodrigues. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Parkinson's disease (PD) is mainly driven by dopaminergic neuronal degeneration in the substantia nigra pars compacta accompanied by chronic neuroinflammation. Despite being mainly sporadic, approximately 10% of all cases are defined as heritable forms of PD, with mutations in the leucine-rich repeat kinase (LRRK2) gene being the most frequent known cause of familial PD. MicroRNAs (miRNAs or miRs), including miR-335, are frequently deregulated in neurodegenerative diseases, such as PD. Here, we aimed to dissect the protective role of miR-335 during inflammation and/or neurodegenerative events in experimental models of PD. Our results showed that miR-335 is significantly downregulated in different PD-mimicking conditions, including BV2 microglia cells stimulated with lipopolysaccharide (LPS) and/or overexpressing wild-type LRRK2. Importantly, these results were confirmed in serum of mice injected with 1-methyl-1-4-phenyl-1,2,3,6-tetrahydripyridine hydrochloride (MPTP), and further validated in patients with idiopathic PD (iPD) and those harboring mutations in LRRK2 (LRRK2-PD), thus corroborating potential clinical relevance. Mechanistically, miR-335 directly targeted LRRK2 mRNA. In the BV2 and N9 microglia cell lines, miR-335 strongly counteracted LPS-induced proinflammatory gene expression, and downregulated receptor interacting protein 1 (RIP1) and RIP3, two important players of necroptotic and inflammatory signaling pathways. Further, miR-335 inhibited LPS-mediated ERK1/2 activation. LRRK2-Wt-induced proinflammatory gene expression was also significantly reduced by miR-335 overexpression. Finally, in SH-SY5Y neuroblastoma cells, miR-335 decreased the expression of pro-inflammatory genes triggered by α-synuclein. In conclusion, we revealed novel roles for miR-335 in both microglia and neuronal cells that strongly halt the effects of classical inflammatory stimuli or LRRK2-Wt overexpression, thus attenuating chronic neuroinflammation.This research was funded in part by UIDB/04138/2020 from Fundação para a Ciência e Tecnologia (FCT), Portugal. SO received a Ph.D. fellowship (PD/BD/128332/2017) from FCT.FrontiersRepositório da Universidade de LisboaOliveira, SaraDionísio, Pedro A.Gaspar, Maria ManuelaCorreia Guedes, LeonorCoelho, MiguelRosa, Mário MiguelFerreira, Joaquim JAmaral, Joana D.Rodrigues, Cecília M. P.2021-09-27T15:43:53Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/49651engFront. Cell Dev. Biol. 9:661461.10.3389/fcell.2021.6614612296-634Xinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-11-20T18:09:18Zoai:repositorio.ul.pt:10451/49651Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-11-20T18:09:18Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv miR-335 targets LRRK2 and mitigates inflammation in Parkinson’s disease
title miR-335 targets LRRK2 and mitigates inflammation in Parkinson’s disease
spellingShingle miR-335 targets LRRK2 and mitigates inflammation in Parkinson’s disease
Oliveira, Sara
LRRK2
Parkinson’s disease
Inflammation
miR-335
Necroptosis
title_short miR-335 targets LRRK2 and mitigates inflammation in Parkinson’s disease
title_full miR-335 targets LRRK2 and mitigates inflammation in Parkinson’s disease
title_fullStr miR-335 targets LRRK2 and mitigates inflammation in Parkinson’s disease
title_full_unstemmed miR-335 targets LRRK2 and mitigates inflammation in Parkinson’s disease
title_sort miR-335 targets LRRK2 and mitigates inflammation in Parkinson’s disease
author Oliveira, Sara
author_facet Oliveira, Sara
Dionísio, Pedro A.
Gaspar, Maria Manuela
Correia Guedes, Leonor
Coelho, Miguel
Rosa, Mário Miguel
Ferreira, Joaquim J
Amaral, Joana D.
Rodrigues, Cecília M. P.
author_role author
author2 Dionísio, Pedro A.
Gaspar, Maria Manuela
Correia Guedes, Leonor
Coelho, Miguel
Rosa, Mário Miguel
Ferreira, Joaquim J
Amaral, Joana D.
Rodrigues, Cecília M. P.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Oliveira, Sara
Dionísio, Pedro A.
Gaspar, Maria Manuela
Correia Guedes, Leonor
Coelho, Miguel
Rosa, Mário Miguel
Ferreira, Joaquim J
Amaral, Joana D.
Rodrigues, Cecília M. P.
dc.subject.por.fl_str_mv LRRK2
Parkinson’s disease
Inflammation
miR-335
Necroptosis
topic LRRK2
Parkinson’s disease
Inflammation
miR-335
Necroptosis
description Copyright © 2021 Oliveira, Dionísio, Gaspar, Correia Guedes, Coelho, Rosa, Ferreira, Amaral and Rodrigues. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
publishDate 2021
dc.date.none.fl_str_mv 2021-09-27T15:43:53Z
2021
2021-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/49651
url http://hdl.handle.net/10451/49651
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Front. Cell Dev. Biol. 9:661461.
10.3389/fcell.2021.661461
2296-634X
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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