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Age-Related microRNA Overexpression in Lafora Disease Male Mice Provides Links between Neuroinflammation and Oxidative Stress

Lafora disease is a rare, fatal form of progressive myoclonus epilepsy characterized by continuous neurodegeneration with epileptic seizures, characterized by the intracellular accumulation of aberrant polyglucosan granules called Lafora bodies. Several works have provided numerous evidence of molec...

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Autores principales: Romá-Mateo, Carlos, Lorente-Pozo, Sheila, Márquez-Thibaut, Lucía, Moreno-Estellés, Mireia, Garcés, Concepción, González, Daymé, Lahuerta, Marcos, Aguado, Carmen, García-Giménez, José Luis, Sanz, Pascual, Pallardó, Federico V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865572/
https://www.ncbi.nlm.nih.gov/pubmed/36674605
http://dx.doi.org/10.3390/ijms24021089
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author Romá-Mateo, Carlos
Lorente-Pozo, Sheila
Márquez-Thibaut, Lucía
Moreno-Estellés, Mireia
Garcés, Concepción
González, Daymé
Lahuerta, Marcos
Aguado, Carmen
García-Giménez, José Luis
Sanz, Pascual
Pallardó, Federico V.
author_facet Romá-Mateo, Carlos
Lorente-Pozo, Sheila
Márquez-Thibaut, Lucía
Moreno-Estellés, Mireia
Garcés, Concepción
González, Daymé
Lahuerta, Marcos
Aguado, Carmen
García-Giménez, José Luis
Sanz, Pascual
Pallardó, Federico V.
author_sort Romá-Mateo, Carlos
collection PubMed
description Lafora disease is a rare, fatal form of progressive myoclonus epilepsy characterized by continuous neurodegeneration with epileptic seizures, characterized by the intracellular accumulation of aberrant polyglucosan granules called Lafora bodies. Several works have provided numerous evidence of molecular and cellular alterations in neural tissue from experimental mouse models deficient in either laforin or malin, two proteins related to the disease. Oxidative stress, alterations in proteostasis, and deregulation of inflammatory signals are some of the molecular alterations underlying this condition in both KO animal models. Lafora bodies appear early in the animal’s life, but many of the aforementioned molecular aberrant processes and the consequent neurological symptoms ensue only as animals age. Here, using small RNA-seq and quantitative PCR on brain extracts from laforin and malin KO male mice of different ages, we show that two different microRNA species, miR-155 and miR-146a, are overexpressed in an age-dependent manner. We also observed altered expression of putative target genes for each of the microRNAs studied in brain extracts. These results open the path for a detailed dissection of the molecular consequences of laforin and malin deficiency in brain tissue, as well as the potential role of miR-155 and miR-146a as specific biomarkers of disease progression in LD.
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spelling pubmed-98655722023-01-22 Age-Related microRNA Overexpression in Lafora Disease Male Mice Provides Links between Neuroinflammation and Oxidative Stress Romá-Mateo, Carlos Lorente-Pozo, Sheila Márquez-Thibaut, Lucía Moreno-Estellés, Mireia Garcés, Concepción González, Daymé Lahuerta, Marcos Aguado, Carmen García-Giménez, José Luis Sanz, Pascual Pallardó, Federico V. Int J Mol Sci Communication Lafora disease is a rare, fatal form of progressive myoclonus epilepsy characterized by continuous neurodegeneration with epileptic seizures, characterized by the intracellular accumulation of aberrant polyglucosan granules called Lafora bodies. Several works have provided numerous evidence of molecular and cellular alterations in neural tissue from experimental mouse models deficient in either laforin or malin, two proteins related to the disease. Oxidative stress, alterations in proteostasis, and deregulation of inflammatory signals are some of the molecular alterations underlying this condition in both KO animal models. Lafora bodies appear early in the animal’s life, but many of the aforementioned molecular aberrant processes and the consequent neurological symptoms ensue only as animals age. Here, using small RNA-seq and quantitative PCR on brain extracts from laforin and malin KO male mice of different ages, we show that two different microRNA species, miR-155 and miR-146a, are overexpressed in an age-dependent manner. We also observed altered expression of putative target genes for each of the microRNAs studied in brain extracts. These results open the path for a detailed dissection of the molecular consequences of laforin and malin deficiency in brain tissue, as well as the potential role of miR-155 and miR-146a as specific biomarkers of disease progression in LD. MDPI 2023-01-06 /pmc/articles/PMC9865572/ /pubmed/36674605 http://dx.doi.org/10.3390/ijms24021089 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Romá-Mateo, Carlos
Lorente-Pozo, Sheila
Márquez-Thibaut, Lucía
Moreno-Estellés, Mireia
Garcés, Concepción
González, Daymé
Lahuerta, Marcos
Aguado, Carmen
García-Giménez, José Luis
Sanz, Pascual
Pallardó, Federico V.
Age-Related microRNA Overexpression in Lafora Disease Male Mice Provides Links between Neuroinflammation and Oxidative Stress
title Age-Related microRNA Overexpression in Lafora Disease Male Mice Provides Links between Neuroinflammation and Oxidative Stress
title_full Age-Related microRNA Overexpression in Lafora Disease Male Mice Provides Links between Neuroinflammation and Oxidative Stress
title_fullStr Age-Related microRNA Overexpression in Lafora Disease Male Mice Provides Links between Neuroinflammation and Oxidative Stress
title_full_unstemmed Age-Related microRNA Overexpression in Lafora Disease Male Mice Provides Links between Neuroinflammation and Oxidative Stress
title_short Age-Related microRNA Overexpression in Lafora Disease Male Mice Provides Links between Neuroinflammation and Oxidative Stress
title_sort age-related microrna overexpression in lafora disease male mice provides links between neuroinflammation and oxidative stress
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865572/
https://www.ncbi.nlm.nih.gov/pubmed/36674605
http://dx.doi.org/10.3390/ijms24021089
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