Altered regulation of KIAA0566, and katanin signaling expression in the locus coeruleus with neurofibrillary tangle pathology

The locus coeruleus (LC), which contains the largest group of noradrenergic neurons in the central nervous system innervating the telencephalon, is an early and constantly vulnerable region to neurofibrillary tangle (NFT) pathology in aging and Alzheimer's disease (AD). The present study using...

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Autores: Andrés Benito, Pol, Delgado-Morales, Raul, Ferrer, Isidro (Ferrer Abizanda)
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
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:2445/140699
Acceso en línea:https://hdl.handle.net/2445/140699
Access Level:acceso abierto
Palabra clave:Malaltia d'Alzheimer
Metilació
Microtúbuls
Alzheimer's disease
Methylation
Microtubules
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spelling Altered regulation of KIAA0566, and katanin signaling expression in the locus coeruleus with neurofibrillary tangle pathologyAndrés Benito, PolDelgado-Morales, RaulFerrer, Isidro (Ferrer Abizanda)Malaltia d'AlzheimerMetilacióMicrotúbulsAlzheimer's diseaseMethylationMicrotubulesThe locus coeruleus (LC), which contains the largest group of noradrenergic neurons in the central nervous system innervating the telencephalon, is an early and constantly vulnerable region to neurofibrillary tangle (NFT) pathology in aging and Alzheimer's disease (AD). The present study using whole genome bisulfite sequencing and Infinium Human Methylation 450 BeadChip was designed to learn about DNA methylation profiles in LC with age and NFT pathology. This method identified decreased DNA methylation of Katanin-Interacting Protein gene (KIAA0566) linked to age and presence of NFT pathology. KIAA0566 mRNA expression demonstrated with RT-qPCR significantly decreased in cases with NFT pathology. Importantly, KIAA0566 immunoreactivity was significantly decreased only in LC neurons with NFTs, but not in neurons without tau pathology when compared with neurons of middle-aged individuals. These changes were accompanied by a similar pattern of selective p80-katanin reduced protein expression in neurons with NFTs. In contrast, p60-katanin subunit expression levels in the neuropil were similar in MA cases and cases with NFT pathology. Since katanin is a major microtubule-severing protein and KIAA0566 binds and interacts with katanin, de-regulation of the katanin-signaling pathway may have implications in the regulation of microtubule homeostasis in LC neurons with NFTs, thereby potentially interfering with maintenance of the cytoskeleton and transport. Keywords: Alzheimer's disease, locus coeruleus, neurofibrillary tangles, methylation, katanin, KIAA0556, microtubulesFrontiers Media2019201920182019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/140699Articles publicats en revistes (Patologia i Terapèutica Experimental)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/10.3389/fncel.2018.00131Frontiers in Cellular Neuroscience, 2018, vol. 12, p. 131https://doi.org/10.3389/fncel.2018.00131cc-by (c) Andrés Benito, Pol et al., 2018http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1406992026-05-29T05:05:01Z
dc.title.none.fl_str_mv Altered regulation of KIAA0566, and katanin signaling expression in the locus coeruleus with neurofibrillary tangle pathology
title Altered regulation of KIAA0566, and katanin signaling expression in the locus coeruleus with neurofibrillary tangle pathology
spellingShingle Altered regulation of KIAA0566, and katanin signaling expression in the locus coeruleus with neurofibrillary tangle pathology
Andrés Benito, Pol
Malaltia d'Alzheimer
Metilació
Microtúbuls
Alzheimer's disease
Methylation
Microtubules
title_short Altered regulation of KIAA0566, and katanin signaling expression in the locus coeruleus with neurofibrillary tangle pathology
title_full Altered regulation of KIAA0566, and katanin signaling expression in the locus coeruleus with neurofibrillary tangle pathology
title_fullStr Altered regulation of KIAA0566, and katanin signaling expression in the locus coeruleus with neurofibrillary tangle pathology
title_full_unstemmed Altered regulation of KIAA0566, and katanin signaling expression in the locus coeruleus with neurofibrillary tangle pathology
title_sort Altered regulation of KIAA0566, and katanin signaling expression in the locus coeruleus with neurofibrillary tangle pathology
dc.creator.none.fl_str_mv Andrés Benito, Pol
Delgado-Morales, Raul
Ferrer, Isidro (Ferrer Abizanda)
author Andrés Benito, Pol
author_facet Andrés Benito, Pol
Delgado-Morales, Raul
Ferrer, Isidro (Ferrer Abizanda)
author_role author
author2 Delgado-Morales, Raul
Ferrer, Isidro (Ferrer Abizanda)
author2_role author
author
dc.subject.none.fl_str_mv Malaltia d'Alzheimer
Metilació
Microtúbuls
Alzheimer's disease
Methylation
Microtubules
topic Malaltia d'Alzheimer
Metilació
Microtúbuls
Alzheimer's disease
Methylation
Microtubules
description The locus coeruleus (LC), which contains the largest group of noradrenergic neurons in the central nervous system innervating the telencephalon, is an early and constantly vulnerable region to neurofibrillary tangle (NFT) pathology in aging and Alzheimer's disease (AD). The present study using whole genome bisulfite sequencing and Infinium Human Methylation 450 BeadChip was designed to learn about DNA methylation profiles in LC with age and NFT pathology. This method identified decreased DNA methylation of Katanin-Interacting Protein gene (KIAA0566) linked to age and presence of NFT pathology. KIAA0566 mRNA expression demonstrated with RT-qPCR significantly decreased in cases with NFT pathology. Importantly, KIAA0566 immunoreactivity was significantly decreased only in LC neurons with NFTs, but not in neurons without tau pathology when compared with neurons of middle-aged individuals. These changes were accompanied by a similar pattern of selective p80-katanin reduced protein expression in neurons with NFTs. In contrast, p60-katanin subunit expression levels in the neuropil were similar in MA cases and cases with NFT pathology. Since katanin is a major microtubule-severing protein and KIAA0566 binds and interacts with katanin, de-regulation of the katanin-signaling pathway may have implications in the regulation of microtubule homeostasis in LC neurons with NFTs, thereby potentially interfering with maintenance of the cytoskeleton and transport. Keywords: Alzheimer's disease, locus coeruleus, neurofibrillary tangles, methylation, katanin, KIAA0556, microtubules
publishDate 2018
dc.date.none.fl_str_mv 2018
2019
2019
2019
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/2445/140699
url https://hdl.handle.net/2445/140699
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/10.3389/fncel.2018.00131
Frontiers in Cellular Neuroscience, 2018, vol. 12, p. 131
https://doi.org/10.3389/fncel.2018.00131
dc.rights.none.fl_str_mv cc-by (c) Andrés Benito, Pol et al., 2018
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Andrés Benito, Pol et al., 2018
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
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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