Lack of p62 Impairs Glycogen Aggregation and Exacerbates Pathology in a Mouse Model of Myoclonic Epilepsy of Lafora

Lafora disease (LD) is a fatal childhood-onset dementia characterized by the extensive accumulation of glycogen aggregates-the so-called Lafora Bodies (LBs)-in several organs. The accumulation of LBs in the brain underlies the neurological phenotype of the disease. LBs are composed of abnormal glyco...

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Autores: Pellegrini, Pasquale, Hervera Abad, Arnau, Varea, Olga, Brewer, M. Kathryn, López-Soldado Fernández, Iliana, Guitart, Anna, Aguilera, Mònica, Prats, Neus, Río Fernández, José Antonio del, Guinovart, Joan J. (Joan Josep), 1947-, Duran, Jordi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/189692
Acceso en línea:https://hdl.handle.net/2445/189692
Access Level:acceso abierto
Palabra clave:Glicogen
Epilèpsia
Glycogen
Epilepsy
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spelling Lack of p62 Impairs Glycogen Aggregation and Exacerbates Pathology in a Mouse Model of Myoclonic Epilepsy of LaforaPellegrini, PasqualeHervera Abad, ArnauVarea, OlgaBrewer, M. KathrynLópez-Soldado Fernández, IlianaGuitart, AnnaAguilera, MònicaPrats, NeusRío Fernández, José Antonio delGuinovart, Joan J. (Joan Josep), 1947-Duran, JordiGlicogenEpilèpsiaGlycogenEpilepsyLafora disease (LD) is a fatal childhood-onset dementia characterized by the extensive accumulation of glycogen aggregates-the so-called Lafora Bodies (LBs)-in several organs. The accumulation of LBs in the brain underlies the neurological phenotype of the disease. LBs are composed of abnormal glycogen and various associated proteins, including p62, an autophagy adaptor that participates in the aggregation and clearance of misfolded proteins. To study the role of p62 in the formation of LBs and its participation in the pathology of LD, we generated a mouse model of the disease (malinKO) lacking p62. Deletion of p62 prevented LB accumulation in skeletal muscle and cardiac tissue. In the brain, the absence of p62 altered LB morphology and increased susceptibility to epilepsy. These results demonstrate that p62 participates in the formation of LBs and suggest that the sequestration of abnormal glycogen into LBs is a protective mechanism through which it reduces the deleterious consequences of its accumulation in the brain.Humana Press.2022202220212022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion16 p.application/pdfhttps://hdl.handle.net/2445/189692Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1007/s12035-021-02682-6Molecular Neurobiology, 2021, vol. 59, num. 2, p. 1214-1229https://doi.org/10.1007/s12035-021-02682-6cc-by (c) Pellegrini, Pasquale et al., 2021http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1896922026-05-29T05:05:01Z
dc.title.none.fl_str_mv Lack of p62 Impairs Glycogen Aggregation and Exacerbates Pathology in a Mouse Model of Myoclonic Epilepsy of Lafora
title Lack of p62 Impairs Glycogen Aggregation and Exacerbates Pathology in a Mouse Model of Myoclonic Epilepsy of Lafora
spellingShingle Lack of p62 Impairs Glycogen Aggregation and Exacerbates Pathology in a Mouse Model of Myoclonic Epilepsy of Lafora
Pellegrini, Pasquale
Glicogen
Epilèpsia
Glycogen
Epilepsy
title_short Lack of p62 Impairs Glycogen Aggregation and Exacerbates Pathology in a Mouse Model of Myoclonic Epilepsy of Lafora
title_full Lack of p62 Impairs Glycogen Aggregation and Exacerbates Pathology in a Mouse Model of Myoclonic Epilepsy of Lafora
title_fullStr Lack of p62 Impairs Glycogen Aggregation and Exacerbates Pathology in a Mouse Model of Myoclonic Epilepsy of Lafora
title_full_unstemmed Lack of p62 Impairs Glycogen Aggregation and Exacerbates Pathology in a Mouse Model of Myoclonic Epilepsy of Lafora
title_sort Lack of p62 Impairs Glycogen Aggregation and Exacerbates Pathology in a Mouse Model of Myoclonic Epilepsy of Lafora
dc.creator.none.fl_str_mv Pellegrini, Pasquale
Hervera Abad, Arnau
Varea, Olga
Brewer, M. Kathryn
López-Soldado Fernández, Iliana
Guitart, Anna
Aguilera, Mònica
Prats, Neus
Río Fernández, José Antonio del
Guinovart, Joan J. (Joan Josep), 1947-
Duran, Jordi
author Pellegrini, Pasquale
author_facet Pellegrini, Pasquale
Hervera Abad, Arnau
Varea, Olga
Brewer, M. Kathryn
López-Soldado Fernández, Iliana
Guitart, Anna
Aguilera, Mònica
Prats, Neus
Río Fernández, José Antonio del
Guinovart, Joan J. (Joan Josep), 1947-
Duran, Jordi
author_role author
author2 Hervera Abad, Arnau
Varea, Olga
Brewer, M. Kathryn
López-Soldado Fernández, Iliana
Guitart, Anna
Aguilera, Mònica
Prats, Neus
Río Fernández, José Antonio del
Guinovart, Joan J. (Joan Josep), 1947-
Duran, Jordi
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Glicogen
Epilèpsia
Glycogen
Epilepsy
topic Glicogen
Epilèpsia
Glycogen
Epilepsy
description Lafora disease (LD) is a fatal childhood-onset dementia characterized by the extensive accumulation of glycogen aggregates-the so-called Lafora Bodies (LBs)-in several organs. The accumulation of LBs in the brain underlies the neurological phenotype of the disease. LBs are composed of abnormal glycogen and various associated proteins, including p62, an autophagy adaptor that participates in the aggregation and clearance of misfolded proteins. To study the role of p62 in the formation of LBs and its participation in the pathology of LD, we generated a mouse model of the disease (malinKO) lacking p62. Deletion of p62 prevented LB accumulation in skeletal muscle and cardiac tissue. In the brain, the absence of p62 altered LB morphology and increased susceptibility to epilepsy. These results demonstrate that p62 participates in the formation of LBs and suggest that the sequestration of abnormal glycogen into LBs is a protective mechanism through which it reduces the deleterious consequences of its accumulation in the brain.
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/189692
url https://hdl.handle.net/2445/189692
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1007/s12035-021-02682-6
Molecular Neurobiology, 2021, vol. 59, num. 2, p. 1214-1229
https://doi.org/10.1007/s12035-021-02682-6
dc.rights.none.fl_str_mv cc-by (c) Pellegrini, Pasquale et al., 2021
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Pellegrini, Pasquale et al., 2021
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 16 p.
application/pdf
dc.publisher.none.fl_str_mv Humana Press.
publisher.none.fl_str_mv Humana Press.
dc.source.none.fl_str_mv Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.198674

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