Characterization of ApoJ-reconstituted high-density lipoprotein (rHDL) nanodisc for the potential treatment of cerebral β-amyloidosis

Abstract Cerebral β-amyloidosis is a major feature of Alzheimer’s disease (AD), characterized by the accumulation of β-amyloid protein (Aβ) in the brain. Several studies have implicated lipid/lipoprotein metabolism in the regulation of β-amyloidosis. In this regard, HDL (High Density Lipoprotein)-ba...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sofía Fernández-de-Retana, Mary Cano-Sarabia, Paula Marazuela, Jose Luis Sánchez-Quesada, Annabel Garcia-Leon, Alex Montañola, Joan Montaner, Daniel Maspoch, Mar Hernández-Guillamon
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8ea237bfff65468695d651045054d123
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8ea237bfff65468695d651045054d123
record_format	dspace
spelling	oai:doaj.org-article:8ea237bfff65468695d651045054d1232021-12-02T15:06:02ZCharacterization of ApoJ-reconstituted high-density lipoprotein (rHDL) nanodisc for the potential treatment of cerebral β-amyloidosis10.1038/s41598-017-15215-w2045-2322https://doaj.org/article/8ea237bfff65468695d651045054d1232017-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-15215-whttps://doaj.org/toc/2045-2322Abstract Cerebral β-amyloidosis is a major feature of Alzheimer’s disease (AD), characterized by the accumulation of β-amyloid protein (Aβ) in the brain. Several studies have implicated lipid/lipoprotein metabolism in the regulation of β-amyloidosis. In this regard, HDL (High Density Lipoprotein)-based therapies could ameliorate pathological features associated with AD. As apolipoprotein J (ApoJ) is a natural chaperone that interacts with Aβ, avoiding its aggregation and toxicity, in this study we propose to prepare reconstituted rHDL-rApoJ nanoparticles by assembling phospholipids with recombinant human ApoJ (rApoJ). Hence, rHDL particles were prepared using the cholate dialysis method and characterized by N-PAGE, dynamic light scattering, circular dichroism and electron transmission microscopy. The preparation of rHDL particles showed two-sized populations with discoidal shape. Functionally, rHDL-rApoJ maintained the ability to prevent the Aβ fibrillization and mediated a higher cholesterol efflux from cultured macrophages. Fluorescently-labelled rHDL-rApoJ nanoparticles were intravenously administrated in mice and their distribution over time was determined using an IVIS Xenogen® imager. It was confirmed that rHDL-rApoJ accumulated in the cranial region, especially in old transgenic mice presenting a high cerebral Aβ load. In conclusion, we have standardized a reproducible protocol to produce rHDL-rApoJ nanoparticles, which may be potentially considered as a therapeutic option for β-amyloid-related pathologies.Sofía Fernández-de-RetanaMary Cano-SarabiaPaula MarazuelaJose Luis Sánchez-QuesadaAnnabel Garcia-LeonAlex MontañolaJoan MontanerDaniel MaspochMar Hernández-GuillamonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sofía Fernández-de-Retana Mary Cano-Sarabia Paula Marazuela Jose Luis Sánchez-Quesada Annabel Garcia-Leon Alex Montañola Joan Montaner Daniel Maspoch Mar Hernández-Guillamon Characterization of ApoJ-reconstituted high-density lipoprotein (rHDL) nanodisc for the potential treatment of cerebral β-amyloidosis
description	Abstract Cerebral β-amyloidosis is a major feature of Alzheimer’s disease (AD), characterized by the accumulation of β-amyloid protein (Aβ) in the brain. Several studies have implicated lipid/lipoprotein metabolism in the regulation of β-amyloidosis. In this regard, HDL (High Density Lipoprotein)-based therapies could ameliorate pathological features associated with AD. As apolipoprotein J (ApoJ) is a natural chaperone that interacts with Aβ, avoiding its aggregation and toxicity, in this study we propose to prepare reconstituted rHDL-rApoJ nanoparticles by assembling phospholipids with recombinant human ApoJ (rApoJ). Hence, rHDL particles were prepared using the cholate dialysis method and characterized by N-PAGE, dynamic light scattering, circular dichroism and electron transmission microscopy. The preparation of rHDL particles showed two-sized populations with discoidal shape. Functionally, rHDL-rApoJ maintained the ability to prevent the Aβ fibrillization and mediated a higher cholesterol efflux from cultured macrophages. Fluorescently-labelled rHDL-rApoJ nanoparticles were intravenously administrated in mice and their distribution over time was determined using an IVIS Xenogen® imager. It was confirmed that rHDL-rApoJ accumulated in the cranial region, especially in old transgenic mice presenting a high cerebral Aβ load. In conclusion, we have standardized a reproducible protocol to produce rHDL-rApoJ nanoparticles, which may be potentially considered as a therapeutic option for β-amyloid-related pathologies.
format	article
author	Sofía Fernández-de-Retana Mary Cano-Sarabia Paula Marazuela Jose Luis Sánchez-Quesada Annabel Garcia-Leon Alex Montañola Joan Montaner Daniel Maspoch Mar Hernández-Guillamon
author_facet	Sofía Fernández-de-Retana Mary Cano-Sarabia Paula Marazuela Jose Luis Sánchez-Quesada Annabel Garcia-Leon Alex Montañola Joan Montaner Daniel Maspoch Mar Hernández-Guillamon
author_sort	Sofía Fernández-de-Retana
title	Characterization of ApoJ-reconstituted high-density lipoprotein (rHDL) nanodisc for the potential treatment of cerebral β-amyloidosis
title_short	Characterization of ApoJ-reconstituted high-density lipoprotein (rHDL) nanodisc for the potential treatment of cerebral β-amyloidosis
title_full	Characterization of ApoJ-reconstituted high-density lipoprotein (rHDL) nanodisc for the potential treatment of cerebral β-amyloidosis
title_fullStr	Characterization of ApoJ-reconstituted high-density lipoprotein (rHDL) nanodisc for the potential treatment of cerebral β-amyloidosis
title_full_unstemmed	Characterization of ApoJ-reconstituted high-density lipoprotein (rHDL) nanodisc for the potential treatment of cerebral β-amyloidosis
title_sort	characterization of apoj-reconstituted high-density lipoprotein (rhdl) nanodisc for the potential treatment of cerebral β-amyloidosis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8ea237bfff65468695d651045054d123
work_keys_str_mv	AT sofiafernandezderetana characterizationofapojreconstitutedhighdensitylipoproteinrhdlnanodiscforthepotentialtreatmentofcerebralbamyloidosis AT marycanosarabia characterizationofapojreconstitutedhighdensitylipoproteinrhdlnanodiscforthepotentialtreatmentofcerebralbamyloidosis AT paulamarazuela characterizationofapojreconstitutedhighdensitylipoproteinrhdlnanodiscforthepotentialtreatmentofcerebralbamyloidosis AT joseluissanchezquesada characterizationofapojreconstitutedhighdensitylipoproteinrhdlnanodiscforthepotentialtreatmentofcerebralbamyloidosis AT annabelgarcialeon characterizationofapojreconstitutedhighdensitylipoproteinrhdlnanodiscforthepotentialtreatmentofcerebralbamyloidosis AT alexmontanola characterizationofapojreconstitutedhighdensitylipoproteinrhdlnanodiscforthepotentialtreatmentofcerebralbamyloidosis AT joanmontaner characterizationofapojreconstitutedhighdensitylipoproteinrhdlnanodiscforthepotentialtreatmentofcerebralbamyloidosis AT danielmaspoch characterizationofapojreconstitutedhighdensitylipoproteinrhdlnanodiscforthepotentialtreatmentofcerebralbamyloidosis AT marhernandezguillamon characterizationofapojreconstitutedhighdensitylipoproteinrhdlnanodiscforthepotentialtreatmentofcerebralbamyloidosis
_version_	1718388596245790720

Characterization of ApoJ-reconstituted high-density lipoprotein (rHDL) nanodisc for the potential treatment of cerebral β-amyloidosis

Ejemplares similares