Lenti-GDNF Gene Therapy Protects Against Alzheimer's Disease-Like Neuropathology in 3xTg-AD Mice and MC65 Cells
Susana Revilla et al.
| Autores: | , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2014 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/124948 |
| Acceso en línea: | http://hdl.handle.net/10261/124948 |
| Access Level: | acceso abierto |
| Palabra clave: | Alzheimer disease Gene therapy Glial cell line-derived neurotrophic factor Neuroblastoma Transgenic mice |
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oai:digital.csic.es:10261/124948 |
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ES |
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España |
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Lenti-GDNF Gene Therapy Protects Against Alzheimer's Disease-Like Neuropathology in 3xTg-AD Mice and MC65 Cells Revilla, Susana Álvarez-López, María Jesús Perpiñá, Unai García-Mesa, Yoelvis Bortolozzi, Analía Kaliman, Perla Cristòfol, Rosa Sanfeliu, Coral Alzheimer disease Gene therapy Glial cell line-derived neurotrophic factor Neuroblastoma Transgenic mice Susana 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 Reviewed Wiley-Blackwell http://hdl.handle.net/10261/124948 |
| 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 |
| 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 |
| topic |
Alzheimer disease Gene therapy Glial cell line-derived neurotrophic factor Neuroblastoma Transgenic mice |
| topic_facet |
Alzheimer disease Gene therapy Glial cell line-derived neurotrophic factor Neuroblastoma Transgenic mice |
| description |
Susana Revilla et al. |
| publishDate |
2014 |
| format |
article |
| status_str |
acceptedVersion |
| url |
http://hdl.handle.net/10261/124948 |
| eu_rights_str_mv |
openAccess |
| publisher |
Wiley-Blackwell |
| institution |
Consejo Superior de Investigaciones Científicas (CSIC) |
| collection |
DIGITAL.CSIC. Repositorio Institucional del CSIC |
| reponame_str |
DIGITAL.CSIC. Repositorio Institucional del CSIC |
| instname_str |
Consejo Superior de Investigaciones Científicas (CSIC) |
| _version_ |
1878441040386457600 |
| publishDateSort |
2014 |
| author_browse |
Bortolozzi, Analía Cristòfol, Rosa García-Mesa, Yoelvis Kaliman, Perla Perpiñá, Unai Revilla, Susana Sanfeliu, Coral Álvarez-López, María Jesús |
| publisherStr |
Wiley-Blackwell |
| score |
6.9303427 |