Cargando…

Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington’s Disease and Human Blood Plasma

(1) Background: Huntington’s disease (HD) is rare incurable hereditary neurodegenerative disorder caused by CAG repeat expansion in the gene coding for the protein huntingtin (HTT). Mutated huntingtin (mHTT) undergoes fragmentation and accumulation, affecting cellular functions and leading to neuron...

Descripción completa

Detalles Bibliográficos
Autores principales: Ananbeh, Hanadi, Novak, Jaromir, Juhas, Stefan, Juhasova, Jana, Klempir, Jiri, Doleckova, Kristyna, Rysankova, Irena, Turnovcova, Karolina, Hanus, Jaroslav, Hansikova, Hana, Vodicka, Petr, Kupcova Skalnikova, Helena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147436/
https://www.ncbi.nlm.nih.gov/pubmed/35628406
http://dx.doi.org/10.3390/ijms23105598
_version_ 1784716807029915648
author Ananbeh, Hanadi
Novak, Jaromir
Juhas, Stefan
Juhasova, Jana
Klempir, Jiri
Doleckova, Kristyna
Rysankova, Irena
Turnovcova, Karolina
Hanus, Jaroslav
Hansikova, Hana
Vodicka, Petr
Kupcova Skalnikova, Helena
author_facet Ananbeh, Hanadi
Novak, Jaromir
Juhas, Stefan
Juhasova, Jana
Klempir, Jiri
Doleckova, Kristyna
Rysankova, Irena
Turnovcova, Karolina
Hanus, Jaroslav
Hansikova, Hana
Vodicka, Petr
Kupcova Skalnikova, Helena
author_sort Ananbeh, Hanadi
collection PubMed
description (1) Background: Huntington’s disease (HD) is rare incurable hereditary neurodegenerative disorder caused by CAG repeat expansion in the gene coding for the protein huntingtin (HTT). Mutated huntingtin (mHTT) undergoes fragmentation and accumulation, affecting cellular functions and leading to neuronal cell death. Porcine models of HD are used in preclinical testing of currently emerging disease modifying therapies. Such therapies are aimed at reducing mHTT expression, postpone the disease onset, slow down the progression, and point out the need of biomarkers to monitor disease development and therapy efficacy. Recently, extracellular vesicles (EVs), particularly exosomes, gained attention as possible carriers of disease biomarkers. We aimed to characterize HTT and mHTT forms/fragments in blood plasma derived EVs in transgenic (TgHD) and knock-in (KI-HD) porcine models, as well as in HD patients’ plasma. (2) Methods: Small EVs were isolated by ultracentrifugation and HTT forms were visualized by western blotting. (3) Results: The full length 360 kDa HTT co-isolated with EVs from both the pig model and HD patient plasma. In addition, a ~70 kDa mutant HTT fragment was specific for TgHD pigs. Elevated total huntingtin levels in EVs from plasma of HD groups compared to controls were observed in both pig models and HD patients, however only in TgHD were they significant (p = 0.02). (4) Conclusions: Our study represents a valuable initial step towards the characterization of EV content in the search for HD biomarkers.
format Online
Article
Text
id pubmed-9147436
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-91474362022-05-29 Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington’s Disease and Human Blood Plasma Ananbeh, Hanadi Novak, Jaromir Juhas, Stefan Juhasova, Jana Klempir, Jiri Doleckova, Kristyna Rysankova, Irena Turnovcova, Karolina Hanus, Jaroslav Hansikova, Hana Vodicka, Petr Kupcova Skalnikova, Helena Int J Mol Sci Article (1) Background: Huntington’s disease (HD) is rare incurable hereditary neurodegenerative disorder caused by CAG repeat expansion in the gene coding for the protein huntingtin (HTT). Mutated huntingtin (mHTT) undergoes fragmentation and accumulation, affecting cellular functions and leading to neuronal cell death. Porcine models of HD are used in preclinical testing of currently emerging disease modifying therapies. Such therapies are aimed at reducing mHTT expression, postpone the disease onset, slow down the progression, and point out the need of biomarkers to monitor disease development and therapy efficacy. Recently, extracellular vesicles (EVs), particularly exosomes, gained attention as possible carriers of disease biomarkers. We aimed to characterize HTT and mHTT forms/fragments in blood plasma derived EVs in transgenic (TgHD) and knock-in (KI-HD) porcine models, as well as in HD patients’ plasma. (2) Methods: Small EVs were isolated by ultracentrifugation and HTT forms were visualized by western blotting. (3) Results: The full length 360 kDa HTT co-isolated with EVs from both the pig model and HD patient plasma. In addition, a ~70 kDa mutant HTT fragment was specific for TgHD pigs. Elevated total huntingtin levels in EVs from plasma of HD groups compared to controls were observed in both pig models and HD patients, however only in TgHD were they significant (p = 0.02). (4) Conclusions: Our study represents a valuable initial step towards the characterization of EV content in the search for HD biomarkers. MDPI 2022-05-17 /pmc/articles/PMC9147436/ /pubmed/35628406 http://dx.doi.org/10.3390/ijms23105598 Text en © 2022 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 Article
Ananbeh, Hanadi
Novak, Jaromir
Juhas, Stefan
Juhasova, Jana
Klempir, Jiri
Doleckova, Kristyna
Rysankova, Irena
Turnovcova, Karolina
Hanus, Jaroslav
Hansikova, Hana
Vodicka, Petr
Kupcova Skalnikova, Helena
Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington’s Disease and Human Blood Plasma
title Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington’s Disease and Human Blood Plasma
title_full Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington’s Disease and Human Blood Plasma
title_fullStr Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington’s Disease and Human Blood Plasma
title_full_unstemmed Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington’s Disease and Human Blood Plasma
title_short Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington’s Disease and Human Blood Plasma
title_sort huntingtin co-isolates with small extracellular vesicles from blood plasma of tghd and ki-hd pig models of huntington’s disease and human blood plasma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147436/
https://www.ncbi.nlm.nih.gov/pubmed/35628406
http://dx.doi.org/10.3390/ijms23105598
work_keys_str_mv AT ananbehhanadi huntingtincoisolateswithsmallextracellularvesiclesfrombloodplasmaoftghdandkihdpigmodelsofhuntingtonsdiseaseandhumanbloodplasma
AT novakjaromir huntingtincoisolateswithsmallextracellularvesiclesfrombloodplasmaoftghdandkihdpigmodelsofhuntingtonsdiseaseandhumanbloodplasma
AT juhasstefan huntingtincoisolateswithsmallextracellularvesiclesfrombloodplasmaoftghdandkihdpigmodelsofhuntingtonsdiseaseandhumanbloodplasma
AT juhasovajana huntingtincoisolateswithsmallextracellularvesiclesfrombloodplasmaoftghdandkihdpigmodelsofhuntingtonsdiseaseandhumanbloodplasma
AT klempirjiri huntingtincoisolateswithsmallextracellularvesiclesfrombloodplasmaoftghdandkihdpigmodelsofhuntingtonsdiseaseandhumanbloodplasma
AT doleckovakristyna huntingtincoisolateswithsmallextracellularvesiclesfrombloodplasmaoftghdandkihdpigmodelsofhuntingtonsdiseaseandhumanbloodplasma
AT rysankovairena huntingtincoisolateswithsmallextracellularvesiclesfrombloodplasmaoftghdandkihdpigmodelsofhuntingtonsdiseaseandhumanbloodplasma
AT turnovcovakarolina huntingtincoisolateswithsmallextracellularvesiclesfrombloodplasmaoftghdandkihdpigmodelsofhuntingtonsdiseaseandhumanbloodplasma
AT hanusjaroslav huntingtincoisolateswithsmallextracellularvesiclesfrombloodplasmaoftghdandkihdpigmodelsofhuntingtonsdiseaseandhumanbloodplasma
AT hansikovahana huntingtincoisolateswithsmallextracellularvesiclesfrombloodplasmaoftghdandkihdpigmodelsofhuntingtonsdiseaseandhumanbloodplasma
AT vodickapetr huntingtincoisolateswithsmallextracellularvesiclesfrombloodplasmaoftghdandkihdpigmodelsofhuntingtonsdiseaseandhumanbloodplasma
AT kupcovaskalnikovahelena huntingtincoisolateswithsmallextracellularvesiclesfrombloodplasmaoftghdandkihdpigmodelsofhuntingtonsdiseaseandhumanbloodplasma