Unraveling targetable systemic and cell-type-specific molecular phenotypes of Alzheimer’s and Parkinson’s brains with digital cytometry

Detalhes bibliográficos
Autor(a) principal: Bordone, Marie C.
Data de Publicação: 2020
Outros Autores: Barbosa-Morais, Nuno
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/47208
Resumo: Copyright © 2020 Bordone and Barbosa-Morais. 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 theoriginal 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 Unraveling targetable systemic and cell-type-specific molecular phenotypes of Alzheimer’s and Parkinson’s brains with digital cytometryAlzheimer’s diseaseParkinson’s diseaseNeurodegenerationCellular deconvolutionDigital cytometrySingle-cell RNA-seqChemo-transcriptomicsCopyright © 2020 Bordone and Barbosa-Morais. 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 theoriginal 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.Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative disorders worldwide, with age being their major risk factor. The increasing worldwide life expectancy, together with the scarcity of available treatment choices, makes it thus pressing to find the molecular basis of AD and PD so that the causing mechanisms can be targeted. To study these mechanisms, gene expression profiles have been compared between diseased and control brain tissues. However, this approach is limited by mRNA expression profiles derived for brain tissues highly reflecting their degeneration in cellular composition but not necessarily disease-related molecular states. We therefore propose to account for cell type composition when comparing transcriptomes of healthy and diseased brain samples, so that the loss of neurons can be decoupled from pathology-associated molecular effects. This approach allowed us to identify genes and pathways putatively altered systemically and in a cell-type-dependent manner in AD and PD brains. Moreover, using chemical perturbagen data, we computationally identified candidate small molecules for specifically targeting the profiled AD/PD-associated molecular alterations. Our approach therefore not only brings new insights into the disease-specific and common molecular etiologies of AD and PD but also, in these realms, foster the discovery of more specific targets for functional and therapeutic exploration.This work was supported by European Molecular Biology Organization (EMBO Installation Grant 3057 to NB-M), Fundação para a Ciência e a Tecnologia (FCT Investigator Starting Grant IF/00595/2014 and CEEC Individual Assistant Researcher contract CEECIND/00436/2018 to NB-M, Ph.D.Studentship PD/BD/105854/2014 to MB), and Genome PT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 – Operational Programme for Competitiveness and Internationalization (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020),under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).FrontiersRepositório da Universidade de LisboaBordone, Marie C.Barbosa-Morais, Nuno2021-04-01T15:46:10Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/47208engFront Neurosci. 2020 Dec 9;14:6072151662-454810.3389/fnins.2020.6072151662-453Xinfo: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:RCAAP2023-11-08T16:49:57Zoai:repositorio.ul.pt:10451/47208Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:59:17.065669Repositório 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 Unraveling targetable systemic and cell-type-specific molecular phenotypes of Alzheimer’s and Parkinson’s brains with digital cytometry
title Unraveling targetable systemic and cell-type-specific molecular phenotypes of Alzheimer’s and Parkinson’s brains with digital cytometry
spellingShingle Unraveling targetable systemic and cell-type-specific molecular phenotypes of Alzheimer’s and Parkinson’s brains with digital cytometry
Bordone, Marie C.
Alzheimer’s disease
Parkinson’s disease
Neurodegeneration
Cellular deconvolution
Digital cytometry
Single-cell RNA-seq
Chemo-transcriptomics
title_short Unraveling targetable systemic and cell-type-specific molecular phenotypes of Alzheimer’s and Parkinson’s brains with digital cytometry
title_full Unraveling targetable systemic and cell-type-specific molecular phenotypes of Alzheimer’s and Parkinson’s brains with digital cytometry
title_fullStr Unraveling targetable systemic and cell-type-specific molecular phenotypes of Alzheimer’s and Parkinson’s brains with digital cytometry
title_full_unstemmed Unraveling targetable systemic and cell-type-specific molecular phenotypes of Alzheimer’s and Parkinson’s brains with digital cytometry
title_sort Unraveling targetable systemic and cell-type-specific molecular phenotypes of Alzheimer’s and Parkinson’s brains with digital cytometry
author Bordone, Marie C.
author_facet Bordone, Marie C.
Barbosa-Morais, Nuno
author_role author
author2 Barbosa-Morais, Nuno
author2_role author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Bordone, Marie C.
Barbosa-Morais, Nuno
dc.subject.por.fl_str_mv Alzheimer’s disease
Parkinson’s disease
Neurodegeneration
Cellular deconvolution
Digital cytometry
Single-cell RNA-seq
Chemo-transcriptomics
topic Alzheimer’s disease
Parkinson’s disease
Neurodegeneration
Cellular deconvolution
Digital cytometry
Single-cell RNA-seq
Chemo-transcriptomics
description Copyright © 2020 Bordone and Barbosa-Morais. 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 theoriginal 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 2020
dc.date.none.fl_str_mv 2020
2020-01-01T00:00:00Z
2021-04-01T15:46:10Z
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/10451/47208
url http://hdl.handle.net/10451/47208
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Front Neurosci. 2020 Dec 9;14:607215
1662-4548
10.3389/fnins.2020.607215
1662-453X
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
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