Recombinant pre-miR-29b for Alzheimer´s disease therapeutics
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/108900 https://doi.org/10.1038/srep19946 |
Resumo: | MicroRNAs are arising as the next generation of diagnostic and therapeutic tools for gene silencing. Studies demonstrated that the miR-29 expression is decreased in Alzheimer's disease (AD) patients displaying high levels of human β-secretase (hBACE1). Recent advances toward an effective therapy for AD intend to employ miR-29 to suppress hBACE1 expression and subsequent Amyloid-β (Aβ) peptide. However, delivery of mature miRNA has demonstrated modest efficacy in vitro; therefore, the preparation of highly pure and biologically active pre-miRNA arises as one of the most important challenges in the development of these therapeutic strategies. Recently, we described a new strategy based arginine-affinity chromatography to specifically purify the recombinant pre-miR-29b. Following this strategy, the purified pre-miR-29b was successfully encapsulated into polyplexes that were further delivered in cytoplasm. It was verified that Chitosan/pre-miR-29b and Polyethylenimine/pre-miR-29b systems efficiently delivered pre-miR-29b to N2a695 cells, thus reducing the hBACE1 protein expression (around 78% and 86%, respectively) and Aβ42 levels (approximately 44% and 47%, respectively). Furthermore, pre-miR-29b downregulates the hBACE1 mRNA expression in 80%. Overall, it was demonstrated that the recombinant pre-miR-29b using polyplexes allowed to decrease the hBACE1 and Aβ42 expression levels, improving the currently available methodologies of miRNA-based therapeutics. |
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Recombinant pre-miR-29b for Alzheimer´s disease therapeuticsAlzheimer DiseaseAmyloid Precursor Protein SecretasesAmyloid beta-PeptidesAspartic Acid EndopeptidasesCell Line, TumorDrug CompoundingGene ExpressionGene Expression RegulationGenetic TherapyHumansMicroRNAsNeuronsRNA InterferenceRNA PrecursorsRNA, MessengerTransfectionMicroRNAs are arising as the next generation of diagnostic and therapeutic tools for gene silencing. Studies demonstrated that the miR-29 expression is decreased in Alzheimer's disease (AD) patients displaying high levels of human β-secretase (hBACE1). Recent advances toward an effective therapy for AD intend to employ miR-29 to suppress hBACE1 expression and subsequent Amyloid-β (Aβ) peptide. However, delivery of mature miRNA has demonstrated modest efficacy in vitro; therefore, the preparation of highly pure and biologically active pre-miRNA arises as one of the most important challenges in the development of these therapeutic strategies. Recently, we described a new strategy based arginine-affinity chromatography to specifically purify the recombinant pre-miR-29b. Following this strategy, the purified pre-miR-29b was successfully encapsulated into polyplexes that were further delivered in cytoplasm. It was verified that Chitosan/pre-miR-29b and Polyethylenimine/pre-miR-29b systems efficiently delivered pre-miR-29b to N2a695 cells, thus reducing the hBACE1 protein expression (around 78% and 86%, respectively) and Aβ42 levels (approximately 44% and 47%, respectively). Furthermore, pre-miR-29b downregulates the hBACE1 mRNA expression in 80%. Overall, it was demonstrated that the recombinant pre-miR-29b using polyplexes allowed to decrease the hBACE1 and Aβ42 expression levels, improving the currently available methodologies of miRNA-based therapeutics.Springer Nature2016-01-28info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/108900http://hdl.handle.net/10316/108900https://doi.org/10.1038/srep19946eng2045-2322Pereira, Patrícia ATomás, Joana FQueiroz, João AFigueiras, Ana R.Sousa, Faniinfo: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:RCAAP2023-09-22T11:36:03Zoai:estudogeral.uc.pt:10316/108900Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:25:08.334567Repositório 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 |
Recombinant pre-miR-29b for Alzheimer´s disease therapeutics |
title |
Recombinant pre-miR-29b for Alzheimer´s disease therapeutics |
spellingShingle |
Recombinant pre-miR-29b for Alzheimer´s disease therapeutics Pereira, Patrícia A Alzheimer Disease Amyloid Precursor Protein Secretases Amyloid beta-Peptides Aspartic Acid Endopeptidases Cell Line, Tumor Drug Compounding Gene Expression Gene Expression Regulation Genetic Therapy Humans MicroRNAs Neurons RNA Interference RNA Precursors RNA, Messenger Transfection |
title_short |
Recombinant pre-miR-29b for Alzheimer´s disease therapeutics |
title_full |
Recombinant pre-miR-29b for Alzheimer´s disease therapeutics |
title_fullStr |
Recombinant pre-miR-29b for Alzheimer´s disease therapeutics |
title_full_unstemmed |
Recombinant pre-miR-29b for Alzheimer´s disease therapeutics |
title_sort |
Recombinant pre-miR-29b for Alzheimer´s disease therapeutics |
author |
Pereira, Patrícia A |
author_facet |
Pereira, Patrícia A Tomás, Joana F Queiroz, João A Figueiras, Ana R. Sousa, Fani |
author_role |
author |
author2 |
Tomás, Joana F Queiroz, João A Figueiras, Ana R. Sousa, Fani |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Pereira, Patrícia A Tomás, Joana F Queiroz, João A Figueiras, Ana R. Sousa, Fani |
dc.subject.por.fl_str_mv |
Alzheimer Disease Amyloid Precursor Protein Secretases Amyloid beta-Peptides Aspartic Acid Endopeptidases Cell Line, Tumor Drug Compounding Gene Expression Gene Expression Regulation Genetic Therapy Humans MicroRNAs Neurons RNA Interference RNA Precursors RNA, Messenger Transfection |
topic |
Alzheimer Disease Amyloid Precursor Protein Secretases Amyloid beta-Peptides Aspartic Acid Endopeptidases Cell Line, Tumor Drug Compounding Gene Expression Gene Expression Regulation Genetic Therapy Humans MicroRNAs Neurons RNA Interference RNA Precursors RNA, Messenger Transfection |
description |
MicroRNAs are arising as the next generation of diagnostic and therapeutic tools for gene silencing. Studies demonstrated that the miR-29 expression is decreased in Alzheimer's disease (AD) patients displaying high levels of human β-secretase (hBACE1). Recent advances toward an effective therapy for AD intend to employ miR-29 to suppress hBACE1 expression and subsequent Amyloid-β (Aβ) peptide. However, delivery of mature miRNA has demonstrated modest efficacy in vitro; therefore, the preparation of highly pure and biologically active pre-miRNA arises as one of the most important challenges in the development of these therapeutic strategies. Recently, we described a new strategy based arginine-affinity chromatography to specifically purify the recombinant pre-miR-29b. Following this strategy, the purified pre-miR-29b was successfully encapsulated into polyplexes that were further delivered in cytoplasm. It was verified that Chitosan/pre-miR-29b and Polyethylenimine/pre-miR-29b systems efficiently delivered pre-miR-29b to N2a695 cells, thus reducing the hBACE1 protein expression (around 78% and 86%, respectively) and Aβ42 levels (approximately 44% and 47%, respectively). Furthermore, pre-miR-29b downregulates the hBACE1 mRNA expression in 80%. Overall, it was demonstrated that the recombinant pre-miR-29b using polyplexes allowed to decrease the hBACE1 and Aβ42 expression levels, improving the currently available methodologies of miRNA-based therapeutics. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-01-28 |
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/10316/108900 http://hdl.handle.net/10316/108900 https://doi.org/10.1038/srep19946 |
url |
http://hdl.handle.net/10316/108900 https://doi.org/10.1038/srep19946 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2045-2322 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
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 |
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1799134134435577856 |