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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Miquel, Ernesto | - |
dc.contributor.author | Villarino, Rosalía | - |
dc.contributor.author | Martínez-Palma, Laura | - |
dc.contributor.author | Cassina, Adriana | - |
dc.contributor.author | Cassina, Patricia | - |
dc.date.accessioned | 2024-04-05T17:59:05Z | - |
dc.date.available | 2024-04-05T17:59:05Z | - |
dc.date.issued | 2024 | - |
dc.identifier.citation | Miquel E, Villarino R, Martínez-Palma L y otros. Pyruvate dehydrogenase kinase 2 knockdown restores the ability of ALS-linked SOD1G93A rat astrocytes to support motor neuron survival by increasing mitochondrial respiration. GLIA [en línea]. 2024; 72(5). 28 p. | es |
dc.identifier.issn | 1098-1136 | - |
dc.identifier.uri | https://hdl.handle.net/20.500.12008/43355 | - |
dc.description | Ernesto Miquel: Departamento de Histología y Embriología - Universidad de la República Facultad de Medicina, Montevideo, Uruguay.-- Rosalía Villarino: Departamento de Histología y Embriología - Universidad de la República Facultad de Medicina, Montevideo, Uruguay.-- Laura Martínez-Palma: Departamento de Histología y Embriología - Universidad de la República Facultad de Medicina, Montevideo, Uruguay.-- Adriana Cassina: Departamento de Bioquímica; Universidad de la República Facultad de Medicina, Centro de Investigaciones Biomédicas (CEINBIO) - Universidad de la República Facultad de Medicina, Montevideo, Uruguay.-- Patricia Cassina: Departamento de Histología y Embriología - Universidad de la República Facultad de Medicina, Montevideo, Uruguay. | es |
dc.description.abstract | Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron (MN) degeneration. Various studies using cellular and animal models of ALS indicate that there is a complex interplay between MN and neighboring non-neuronal cells, such as astrocytes, resulting in noncell autonomous neurodegeneration. Astrocytes in ALS exhibit a lower ability to support MN survival than nondisease-associated ones, which is strongly correlated with low-mitochondrial respiratory activity. Indeed, pharmacological inhibition of pyruvate dehydrogenase kinase (PDK) led to an increase in the mitochondrial oxidative phosphorylation pathway as the primary source of cell energy in SOD1G93A astrocytes and restored the survival of MN. Among the four PDK isoforms, PDK2 is ubiquitously expressed in astrocytes and presents low expression levels in neurons. Herein, we hypothesize whether selective knockdown of PDK2 in astrocytes may increase mitochondrial activity and, in turn, reduce SOD1G93A-associated toxicity. To assess this, cultured neonatal SOD1G93A rat astrocytes were incubated with specific PDK2 siRNA. This treatment resulted in a reduction of the enzyme expression with a concomitant decrease in the phosphorylation rate of the pyruvate dehydrogenase complex. In addition, PDK2-silenced SOD1G93A astrocytes exhibited restored mitochondrial bioenergetics parameters, adopting a more complex mitochondrial network. This treatment also decreased lipid droplet content in SOD1G93A astrocytes, suggesting a switch in energetic metabolism. Significantly, PDK2 knockdown increased the ability of SOD1G93A astrocytes to support MN survival, further supporting the major role of astrocyte mitochondrial respiratory activity in astrocyte-MN interactions. These results suggest that PDK2 silencing could be a cell-specific therapeutic tool to slow the progression of ALS. | es |
dc.format.extent | 28 p. | es |
dc.format.mimetype | application/pdf | es |
dc.language.iso | en | es |
dc.publisher | Wiley | es |
dc.relation.ispartof | GLIA 2024; 72(5) | es |
dc.rights | Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014) | es |
dc.subject | Astrocytes | es |
dc.subject | Neurodegenerative diseases | es |
dc.subject | Metabolic interactions with neurons | es |
dc.subject.other | ASTROCITOS | es |
dc.subject.other | ENFERMEDADES NEURODEGENERATIVAS | es |
dc.subject.other | NEURONAS | es |
dc.title | Pyruvate dehydrogenase kinase 2 knockdown restores the ability of ALS-linked SOD1G93A rat astrocytes to support motor neuron survival by increasing mitochondrial respiration | es |
dc.type | Artículo | es |
dc.contributor.filiacion | Miquel Ernesto, Universidad de la República (Uruguay). Facultad de Medicina | - |
dc.contributor.filiacion | Villarino Rosalía, Universidad de la República (Uruguay). Facultad de Medicina | - |
dc.contributor.filiacion | Martínez-Palma Laura, Universidad de la República (Uruguay). Facultad de Medicina | - |
dc.contributor.filiacion | Cassina Adriana, Universidad de la República (Uruguay). Facultad de Medicina | - |
dc.contributor.filiacion | Cassina Patricia, Universidad de la República (Uruguay). Facultad de Medicina | - |
dc.rights.licence | Licencia Creative Commons Atribución (CC - By 4.0) | es |
dc.identifier.doi | 10.1002/glia.24516 | - |
Aparece en las colecciones: | Publicaciones Académicas y Científicas - Facultad de Medicina |
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Miquel et al 2024GLIA.pdf | Pyruvate dehydrogenase kinase 2 knockdown restores the ability of ALS-linked SOD1G93A rat astrocytes to support motor neuron survival by increasing mitochondrial respiration | 10,67 MB | Adobe PDF | Visualizar/Abrir |
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