Lenti-GDNF Gene Therapy Protects Against Alzheimer's Disease-Like Neuropathology in 3xTg-AD Mice and MC65 Cells

Susana Revilla et al.

Detalhes bibliográficos
Autores: Revilla, Susana, Álvarez-López, María Jesús, Perpiñá, Unai, García-Mesa, Yoelvis, Bortolozzi, Analía, Kaliman, Perla, Cristòfol, Rosa, Sanfeliu, Coral
Tipo de documento: artigo
Estado:Versión aceptada para publicación
Data de publicação:2014
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/124948
Acesso em linha:http://hdl.handle.net/10261/124948
Access Level:Acceso aberto
Palavra-chave:Alzheimer disease
Gene therapy
Glial cell line-derived neurotrophic factor
Neuroblastoma
Transgenic mice
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spelling Lenti-GDNF Gene Therapy Protects Against Alzheimer's Disease-Like Neuropathology in 3xTg-AD Mice and MC65 CellsRevilla, SusanaÁlvarez-López, María JesúsPerpiñá, UnaiGarcía-Mesa, YoelvisBortolozzi, AnalíaKaliman, PerlaCristòfol, RosaSanfeliu, CoralAlzheimer diseaseGene therapyGlial cell line-derived neurotrophic factorNeuroblastomaTransgenic miceSusana Revilla et al.© 2014 John Wiley & Sons Ltd. Summary: Aims: Glial cell-derived neurotrophic factor (GDNF) is emerging as a potent neurotrophic factor with therapeutic potential against a range of neurodegenerative conditions including Alzheimer's disease (AD). We assayed the effects of GDNF treatment in AD experimental models through gene-therapy procedures. Methods: Recombinant lentiviral vectors were used to overexpress GDNF gene in hippocampal astrocytes of 3xTg-AD mice in vivo, and also in the MC65 human neuroblastoma that conditionally overexpresses the 99-residue carboxyl-terminal (C99) fragment of the amyloid precursor protein. Results: After 6 months of overexpressing GDNF, 10-month-old 3xTg-AD mice showed preserved learning and memory, while their counterparts transduced with a green fluorescent protein vector showed cognitive loss. GDNF therapy did not significantly reduce amyloid and tau pathology, but rather, induced a potent upregulation of brain-derived neurotrophic factor that may act in concert with GDNF to protect neurons from atrophy and degeneration. MC65 cells overexpressing GDNF showed an abolishment of oxidative stress and cell death that was at least partially mediated by a reduced presence of intracellular C99 and derived amyloid β oligomers. Conclusions: GDNF induced neuroprotection in the AD experimental models used. Lentiviral vectors engineered to overexpress GDNF showed to be safe and effective, both as a potential gene therapy and as a tool to uncover the mechanisms of GDNF neuroprotection, including cross talk between astrocytes and neurons in the injured brain.Spanish MINECO. Grant Numbers: SAF2009-13093, SAF2012-39852, CSD2010-45; Generalitat. Grant Number: 2009/SGR/214; Fundació La Marató de TV3. Grant Number: 062931; European Regional Development Fund (ERDF)Peer ReviewedWiley-BlackwellGeneralitat de CatalunyaFundació La Marató de TV3Ministerio de Economía y Competitividad (España)European CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2015201520142015info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/124948reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1111/cns.12312Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1249482026-05-22T06:33:51Z
dc.title.none.fl_str_mv Lenti-GDNF Gene Therapy Protects Against Alzheimer's Disease-Like Neuropathology in 3xTg-AD Mice and MC65 Cells
title Lenti-GDNF Gene Therapy Protects Against Alzheimer's Disease-Like Neuropathology in 3xTg-AD Mice and MC65 Cells
spellingShingle Lenti-GDNF Gene Therapy Protects Against Alzheimer's Disease-Like Neuropathology in 3xTg-AD Mice and MC65 Cells
Revilla, Susana
Alzheimer disease
Gene therapy
Glial cell line-derived neurotrophic factor
Neuroblastoma
Transgenic mice
title_short Lenti-GDNF Gene Therapy Protects Against Alzheimer's Disease-Like Neuropathology in 3xTg-AD Mice and MC65 Cells
title_full Lenti-GDNF Gene Therapy Protects Against Alzheimer's Disease-Like Neuropathology in 3xTg-AD Mice and MC65 Cells
title_fullStr Lenti-GDNF Gene Therapy Protects Against Alzheimer's Disease-Like Neuropathology in 3xTg-AD Mice and MC65 Cells
title_full_unstemmed Lenti-GDNF Gene Therapy Protects Against Alzheimer's Disease-Like Neuropathology in 3xTg-AD Mice and MC65 Cells
title_sort Lenti-GDNF Gene Therapy Protects Against Alzheimer's Disease-Like Neuropathology in 3xTg-AD Mice and MC65 Cells
dc.creator.none.fl_str_mv Revilla, Susana
Álvarez-López, María Jesús
Perpiñá, Unai
García-Mesa, Yoelvis
Bortolozzi, Analía
Kaliman, Perla
Cristòfol, Rosa
Sanfeliu, Coral
author Revilla, Susana
author_facet Revilla, Susana
Álvarez-López, María Jesús
Perpiñá, Unai
García-Mesa, Yoelvis
Bortolozzi, Analía
Kaliman, Perla
Cristòfol, Rosa
Sanfeliu, Coral
author_role author
author2 Álvarez-López, María Jesús
Perpiñá, Unai
García-Mesa, Yoelvis
Bortolozzi, Analía
Kaliman, Perla
Cristòfol, Rosa
Sanfeliu, Coral
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Generalitat de Catalunya
Fundació La Marató de TV3
Ministerio de Economía y Competitividad (España)
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Alzheimer disease
Gene therapy
Glial cell line-derived neurotrophic factor
Neuroblastoma
Transgenic mice
topic Alzheimer disease
Gene therapy
Glial cell line-derived neurotrophic factor
Neuroblastoma
Transgenic mice
description Susana Revilla et al.
publishDate 2014
dc.date.none.fl_str_mv 2014
2015
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/124948
url http://hdl.handle.net/10261/124948
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1111/cns.12312
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Wiley-Blackwell
publisher.none.fl_str_mv Wiley-Blackwell
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869420143910584320
score 15,81155

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