DNAJB6b-enriched small extracellular vesicles decrease polyglutamine aggregation in in vitro and in vivo models of Huntington disease

Summary: Huntington disease (HD) is a devastating neurodegenerative disorder characterized by aggregation of huntingtin (HTT) protein containing expanded polyglutamine (polyQ) tracts. DNAJB6, a member of the DNAJ chaperone family, was reported to efficiently inhibit polyQ aggregation in vitro, in ce...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Bhagyashree S. Joshi, Sameh A. Youssef, Reinier Bron, Alain de Bruin, Harm H. Kampinga, Inge S. Zuhorn
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Cell biology Molecular neuroscience Molecular physiology Science Q
Acceso en línea:	https://doaj.org/article/7e72da794b2c4764b06ad74b280ea482
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7e72da794b2c4764b06ad74b280ea482
record_format	dspace
spelling	oai:doaj.org-article:7e72da794b2c4764b06ad74b280ea4822021-11-20T05:09:17ZDNAJB6b-enriched small extracellular vesicles decrease polyglutamine aggregation in in vitro and in vivo models of Huntington disease2589-004210.1016/j.isci.2021.103282https://doaj.org/article/7e72da794b2c4764b06ad74b280ea4822021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012517https://doaj.org/toc/2589-0042Summary: Huntington disease (HD) is a devastating neurodegenerative disorder characterized by aggregation of huntingtin (HTT) protein containing expanded polyglutamine (polyQ) tracts. DNAJB6, a member of the DNAJ chaperone family, was reported to efficiently inhibit polyQ aggregation in vitro, in cell models, and in vivo in flies, xenopus, and mice. For the delivery of exogenous DNAJB6 to the brain, the DNAJB6 needs to be protected against (enzymatic) degradation and show good penetration into brain tissue. Here, we tested the potential of small extracellular vesicles (sEVs) derived from neural stem cells (NSCs) for delivery of DNAJB6 as anti-amyloidogenic cargo. Administration of sEVs isolated from DNAJB6-overexpressing cells to cells expressing expanded polyQ tracts suppressed HTT aggregation. Furthermore, intrathecal injection of DNAJB6-enriched sEVs into R6/2 transgenic HD mice significantly reduced mutant HTT aggregation in the brain. Taken together, our data suggest that sEV-mediated molecular chaperone delivery may hold potential to delay disease onset in HD.Bhagyashree S. JoshiSameh A. YoussefReinier BronAlain de BruinHarm H. KampingaInge S. ZuhornElsevierarticleCell biologyMolecular neuroscienceMolecular physiologyScienceQENiScience, Vol 24, Iss 11, Pp 103282- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cell biology Molecular neuroscience Molecular physiology Science Q
spellingShingle	Cell biology Molecular neuroscience Molecular physiology Science Q Bhagyashree S. Joshi Sameh A. Youssef Reinier Bron Alain de Bruin Harm H. Kampinga Inge S. Zuhorn DNAJB6b-enriched small extracellular vesicles decrease polyglutamine aggregation in in vitro and in vivo models of Huntington disease
description	Summary: Huntington disease (HD) is a devastating neurodegenerative disorder characterized by aggregation of huntingtin (HTT) protein containing expanded polyglutamine (polyQ) tracts. DNAJB6, a member of the DNAJ chaperone family, was reported to efficiently inhibit polyQ aggregation in vitro, in cell models, and in vivo in flies, xenopus, and mice. For the delivery of exogenous DNAJB6 to the brain, the DNAJB6 needs to be protected against (enzymatic) degradation and show good penetration into brain tissue. Here, we tested the potential of small extracellular vesicles (sEVs) derived from neural stem cells (NSCs) for delivery of DNAJB6 as anti-amyloidogenic cargo. Administration of sEVs isolated from DNAJB6-overexpressing cells to cells expressing expanded polyQ tracts suppressed HTT aggregation. Furthermore, intrathecal injection of DNAJB6-enriched sEVs into R6/2 transgenic HD mice significantly reduced mutant HTT aggregation in the brain. Taken together, our data suggest that sEV-mediated molecular chaperone delivery may hold potential to delay disease onset in HD.
format	article
author	Bhagyashree S. Joshi Sameh A. Youssef Reinier Bron Alain de Bruin Harm H. Kampinga Inge S. Zuhorn
author_facet	Bhagyashree S. Joshi Sameh A. Youssef Reinier Bron Alain de Bruin Harm H. Kampinga Inge S. Zuhorn
author_sort	Bhagyashree S. Joshi
title	DNAJB6b-enriched small extracellular vesicles decrease polyglutamine aggregation in in vitro and in vivo models of Huntington disease
title_short	DNAJB6b-enriched small extracellular vesicles decrease polyglutamine aggregation in in vitro and in vivo models of Huntington disease
title_full	DNAJB6b-enriched small extracellular vesicles decrease polyglutamine aggregation in in vitro and in vivo models of Huntington disease
title_fullStr	DNAJB6b-enriched small extracellular vesicles decrease polyglutamine aggregation in in vitro and in vivo models of Huntington disease
title_full_unstemmed	DNAJB6b-enriched small extracellular vesicles decrease polyglutamine aggregation in in vitro and in vivo models of Huntington disease
title_sort	dnajb6b-enriched small extracellular vesicles decrease polyglutamine aggregation in in vitro and in vivo models of huntington disease
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/7e72da794b2c4764b06ad74b280ea482
work_keys_str_mv	AT bhagyashreesjoshi dnajb6benrichedsmallextracellularvesiclesdecreasepolyglutamineaggregationininvitroandinvivomodelsofhuntingtondisease AT samehayoussef dnajb6benrichedsmallextracellularvesiclesdecreasepolyglutamineaggregationininvitroandinvivomodelsofhuntingtondisease AT reinierbron dnajb6benrichedsmallextracellularvesiclesdecreasepolyglutamineaggregationininvitroandinvivomodelsofhuntingtondisease AT alaindebruin dnajb6benrichedsmallextracellularvesiclesdecreasepolyglutamineaggregationininvitroandinvivomodelsofhuntingtondisease AT harmhkampinga dnajb6benrichedsmallextracellularvesiclesdecreasepolyglutamineaggregationininvitroandinvivomodelsofhuntingtondisease AT ingeszuhorn dnajb6benrichedsmallextracellularvesiclesdecreasepolyglutamineaggregationininvitroandinvivomodelsofhuntingtondisease
_version_	1718419550285856768

DNAJB6b-enriched small extracellular vesicles decrease polyglutamine aggregation in in vitro and in vivo models of Huntington disease

Ejemplares similares