Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer's disease
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.mad.2020.111352 http://hdl.handle.net/11449/208875 |
Resumo: | Background: MicroRNAs (miRNAs) emerged as regulatory elements, with up to 70 % of all miRNAs found in the brain, playing key roles in the onset of Alzheimer's disease (AD). Objective: to broadly assess the expression levels of miRNAs in post-mortem brain (PMB) samples of individuals deceased with or without AD. Methods: A high-throughput micmarray platform was used to sketch miRNA samples isolated from superior and middle temporal gyrus of A+T+ AD cases, compared to samples from age- and sex-matched AD-devoid donors, all pulled from the University of Sao Paulo's Brain Biobank. The miRNAs identified by microarray were subjected to validation with specific qRT-PCR assays employing independent PMB samples. Results: The analyses yielded 6 miRNAs differentially expressed (miR-30e_3p; miR-365b_5p; miR-664_3p; miR1202; miR-4286; miR-4449), and their interplay with specific AD-related genes and signaling pathways was explored using bioinformatics analyses (including the KEGG package, mirPath v.3). In the end, 3 miRNAs, 7 target genes and 11 pathways were found closely interrelated and implicated with the AD pathophysiology. Conclusion: A dysregulation on a subset of these miRNAs appear to affect a range of genes (notably PTEN) and pathways (emphasis to PI3K-AKT) so to provide grounds for neuronal death by apoptotic signaling, autophagy and/or oxidative damage. |
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Repositório Institucional da UNESP |
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Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer's diseaseAlzheimer's diseasemicroRNAArray analysisDIANA miRPathBackground: MicroRNAs (miRNAs) emerged as regulatory elements, with up to 70 % of all miRNAs found in the brain, playing key roles in the onset of Alzheimer's disease (AD). Objective: to broadly assess the expression levels of miRNAs in post-mortem brain (PMB) samples of individuals deceased with or without AD. Methods: A high-throughput micmarray platform was used to sketch miRNA samples isolated from superior and middle temporal gyrus of A+T+ AD cases, compared to samples from age- and sex-matched AD-devoid donors, all pulled from the University of Sao Paulo's Brain Biobank. The miRNAs identified by microarray were subjected to validation with specific qRT-PCR assays employing independent PMB samples. Results: The analyses yielded 6 miRNAs differentially expressed (miR-30e_3p; miR-365b_5p; miR-664_3p; miR1202; miR-4286; miR-4449), and their interplay with specific AD-related genes and signaling pathways was explored using bioinformatics analyses (including the KEGG package, mirPath v.3). In the end, 3 miRNAs, 7 target genes and 11 pathways were found closely interrelated and implicated with the AD pathophysiology. Conclusion: A dysregulation on a subset of these miRNAs appear to affect a range of genes (notably PTEN) and pathways (emphasis to PI3K-AKT) so to provide grounds for neuronal death by apoptotic signaling, autophagy and/or oxidative damage.Fundacao de Amparo a Pesquisa do Distrito Federal (FAP-DF)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fed Univ Brasilia UnB, Brasilia, DF, BrazilState Univ Sao Paulo USP, Sao Paulo, SP, BrazilMcGill Univ Hlth Ctr MUHC, Montreal, PQ, CanadaState Univ Sao Paulo USP, Sao Paulo, SP, BrazilFundacao de Amparo a Pesquisa do Distrito Federal (FAP-DF): 193.000.967/2015CNPq: 445692/2014-6CAPES: 001CNPq: 303,540/2019 2Elsevier B.V.Fed Univ Brasilia UnBUniversidade Estadual Paulista (Unesp)McGill Univ Hlth Ctr MUHCHenriques, Adriane D.Machado-Silva, WilcellyLeite, Renata E. P. [UNESP]Suemoto, Claudia K. [UNESP]Leite, Katia R. M. [UNESP]Srougi, Miguel [UNESP]Pereira, Alexandre C. [UNESP]Jacob-Filho, Wilson [UNESP]Nobrega, Otavio T.Brazilian Aging Brain Study Grp2021-06-25T11:23:34Z2021-06-25T11:23:34Z2020-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article9http://dx.doi.org/10.1016/j.mad.2020.111352Mechanisms Of Ageing And Development. Clare: Elsevier Ireland Ltd, v. 191, 9 p., 2020.0047-6374http://hdl.handle.net/11449/20887510.1016/j.mad.2020.111352WOS:000579507600021Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengMechanisms Of Ageing And Developmentinfo:eu-repo/semantics/openAccess2021-10-23T19:23:17Zoai:repositorio.unesp.br:11449/208875Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T17:52:01.909750Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer's disease |
title |
Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer's disease |
spellingShingle |
Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer's disease Henriques, Adriane D. Alzheimer's disease microRNA Array analysis DIANA miRPath |
title_short |
Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer's disease |
title_full |
Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer's disease |
title_fullStr |
Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer's disease |
title_full_unstemmed |
Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer's disease |
title_sort |
Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer's disease |
author |
Henriques, Adriane D. |
author_facet |
Henriques, Adriane D. Machado-Silva, Wilcelly Leite, Renata E. P. [UNESP] Suemoto, Claudia K. [UNESP] Leite, Katia R. M. [UNESP] Srougi, Miguel [UNESP] Pereira, Alexandre C. [UNESP] Jacob-Filho, Wilson [UNESP] Nobrega, Otavio T. Brazilian Aging Brain Study Grp |
author_role |
author |
author2 |
Machado-Silva, Wilcelly Leite, Renata E. P. [UNESP] Suemoto, Claudia K. [UNESP] Leite, Katia R. M. [UNESP] Srougi, Miguel [UNESP] Pereira, Alexandre C. [UNESP] Jacob-Filho, Wilson [UNESP] Nobrega, Otavio T. Brazilian Aging Brain Study Grp |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Fed Univ Brasilia UnB Universidade Estadual Paulista (Unesp) McGill Univ Hlth Ctr MUHC |
dc.contributor.author.fl_str_mv |
Henriques, Adriane D. Machado-Silva, Wilcelly Leite, Renata E. P. [UNESP] Suemoto, Claudia K. [UNESP] Leite, Katia R. M. [UNESP] Srougi, Miguel [UNESP] Pereira, Alexandre C. [UNESP] Jacob-Filho, Wilson [UNESP] Nobrega, Otavio T. Brazilian Aging Brain Study Grp |
dc.subject.por.fl_str_mv |
Alzheimer's disease microRNA Array analysis DIANA miRPath |
topic |
Alzheimer's disease microRNA Array analysis DIANA miRPath |
description |
Background: MicroRNAs (miRNAs) emerged as regulatory elements, with up to 70 % of all miRNAs found in the brain, playing key roles in the onset of Alzheimer's disease (AD). Objective: to broadly assess the expression levels of miRNAs in post-mortem brain (PMB) samples of individuals deceased with or without AD. Methods: A high-throughput micmarray platform was used to sketch miRNA samples isolated from superior and middle temporal gyrus of A+T+ AD cases, compared to samples from age- and sex-matched AD-devoid donors, all pulled from the University of Sao Paulo's Brain Biobank. The miRNAs identified by microarray were subjected to validation with specific qRT-PCR assays employing independent PMB samples. Results: The analyses yielded 6 miRNAs differentially expressed (miR-30e_3p; miR-365b_5p; miR-664_3p; miR1202; miR-4286; miR-4449), and their interplay with specific AD-related genes and signaling pathways was explored using bioinformatics analyses (including the KEGG package, mirPath v.3). In the end, 3 miRNAs, 7 target genes and 11 pathways were found closely interrelated and implicated with the AD pathophysiology. Conclusion: A dysregulation on a subset of these miRNAs appear to affect a range of genes (notably PTEN) and pathways (emphasis to PI3K-AKT) so to provide grounds for neuronal death by apoptotic signaling, autophagy and/or oxidative damage. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-10-01 2021-06-25T11:23:34Z 2021-06-25T11:23:34Z |
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://dx.doi.org/10.1016/j.mad.2020.111352 Mechanisms Of Ageing And Development. Clare: Elsevier Ireland Ltd, v. 191, 9 p., 2020. 0047-6374 http://hdl.handle.net/11449/208875 10.1016/j.mad.2020.111352 WOS:000579507600021 |
url |
http://dx.doi.org/10.1016/j.mad.2020.111352 http://hdl.handle.net/11449/208875 |
identifier_str_mv |
Mechanisms Of Ageing And Development. Clare: Elsevier Ireland Ltd, v. 191, 9 p., 2020. 0047-6374 10.1016/j.mad.2020.111352 WOS:000579507600021 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Mechanisms Of Ageing And Development |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
9 |
dc.publisher.none.fl_str_mv |
Elsevier B.V. |
publisher.none.fl_str_mv |
Elsevier B.V. |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808128868657135616 |