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Reduced Levels of ABCA1 Transporter Are Responsible for the Cholesterol Efflux Impairment in β-Amyloid-Induced Reactive Astrocytes: Potential Rescue from Biomimetic HDLs

The cerebral synthesis of cholesterol is mainly handled by astrocytes, which are also responsible for apoproteins’ synthesis and lipoproteins’ assembly required for the cholesterol transport in the brain parenchyma. In Alzheimer disease (AD), these processes are impaired, likely because of the astro...

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Autores principales: Sierri, Giulia, Dal Magro, Roberta, Vergani, Barbara, Leone, Biagio Eugenio, Formicola, Beatrice, Taiarol, Lorenzo, Fagioli, Stefano, Kravicz, Marcelo, Tremolizzo, Lucio, Calabresi, Laura, Re, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745016/
https://www.ncbi.nlm.nih.gov/pubmed/35008528
http://dx.doi.org/10.3390/ijms23010102
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author Sierri, Giulia
Dal Magro, Roberta
Vergani, Barbara
Leone, Biagio Eugenio
Formicola, Beatrice
Taiarol, Lorenzo
Fagioli, Stefano
Kravicz, Marcelo
Tremolizzo, Lucio
Calabresi, Laura
Re, Francesca
author_facet Sierri, Giulia
Dal Magro, Roberta
Vergani, Barbara
Leone, Biagio Eugenio
Formicola, Beatrice
Taiarol, Lorenzo
Fagioli, Stefano
Kravicz, Marcelo
Tremolizzo, Lucio
Calabresi, Laura
Re, Francesca
author_sort Sierri, Giulia
collection PubMed
description The cerebral synthesis of cholesterol is mainly handled by astrocytes, which are also responsible for apoproteins’ synthesis and lipoproteins’ assembly required for the cholesterol transport in the brain parenchyma. In Alzheimer disease (AD), these processes are impaired, likely because of the astrogliosis, a process characterized by morphological and functional changes in astrocytes. Several ATP-binding cassette transporters expressed by brain cells are involved in the formation of nascent discoidal lipoproteins, but the effect of beta-amyloid (Aβ) assemblies on this process is not fully understood. In this study, we investigated how of Aβ(1-42)-induced astrogliosis affects the metabolism of cholesterol in vitro. We detected an impairment in the cholesterol efflux of reactive astrocytes attributable to reduced levels of ABCA1 transporters that could explain the decreased lipoproteins’ levels detected in AD patients. To approach this issue, we designed biomimetic HDLs and evaluated their performance as cholesterol acceptors. The results demonstrated the ability of apoA-I nanodiscs to cross the blood–brain barrier in vitro and to promote the cholesterol efflux from astrocytes, making them suitable as a potential supportive treatment for AD to compensate the depletion of cerebral HDLs.
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spelling pubmed-87450162022-01-11 Reduced Levels of ABCA1 Transporter Are Responsible for the Cholesterol Efflux Impairment in β-Amyloid-Induced Reactive Astrocytes: Potential Rescue from Biomimetic HDLs Sierri, Giulia Dal Magro, Roberta Vergani, Barbara Leone, Biagio Eugenio Formicola, Beatrice Taiarol, Lorenzo Fagioli, Stefano Kravicz, Marcelo Tremolizzo, Lucio Calabresi, Laura Re, Francesca Int J Mol Sci Article The cerebral synthesis of cholesterol is mainly handled by astrocytes, which are also responsible for apoproteins’ synthesis and lipoproteins’ assembly required for the cholesterol transport in the brain parenchyma. In Alzheimer disease (AD), these processes are impaired, likely because of the astrogliosis, a process characterized by morphological and functional changes in astrocytes. Several ATP-binding cassette transporters expressed by brain cells are involved in the formation of nascent discoidal lipoproteins, but the effect of beta-amyloid (Aβ) assemblies on this process is not fully understood. In this study, we investigated how of Aβ(1-42)-induced astrogliosis affects the metabolism of cholesterol in vitro. We detected an impairment in the cholesterol efflux of reactive astrocytes attributable to reduced levels of ABCA1 transporters that could explain the decreased lipoproteins’ levels detected in AD patients. To approach this issue, we designed biomimetic HDLs and evaluated their performance as cholesterol acceptors. The results demonstrated the ability of apoA-I nanodiscs to cross the blood–brain barrier in vitro and to promote the cholesterol efflux from astrocytes, making them suitable as a potential supportive treatment for AD to compensate the depletion of cerebral HDLs. MDPI 2021-12-22 /pmc/articles/PMC8745016/ /pubmed/35008528 http://dx.doi.org/10.3390/ijms23010102 Text en © 2021 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
Sierri, Giulia
Dal Magro, Roberta
Vergani, Barbara
Leone, Biagio Eugenio
Formicola, Beatrice
Taiarol, Lorenzo
Fagioli, Stefano
Kravicz, Marcelo
Tremolizzo, Lucio
Calabresi, Laura
Re, Francesca
Reduced Levels of ABCA1 Transporter Are Responsible for the Cholesterol Efflux Impairment in β-Amyloid-Induced Reactive Astrocytes: Potential Rescue from Biomimetic HDLs
title Reduced Levels of ABCA1 Transporter Are Responsible for the Cholesterol Efflux Impairment in β-Amyloid-Induced Reactive Astrocytes: Potential Rescue from Biomimetic HDLs
title_full Reduced Levels of ABCA1 Transporter Are Responsible for the Cholesterol Efflux Impairment in β-Amyloid-Induced Reactive Astrocytes: Potential Rescue from Biomimetic HDLs
title_fullStr Reduced Levels of ABCA1 Transporter Are Responsible for the Cholesterol Efflux Impairment in β-Amyloid-Induced Reactive Astrocytes: Potential Rescue from Biomimetic HDLs
title_full_unstemmed Reduced Levels of ABCA1 Transporter Are Responsible for the Cholesterol Efflux Impairment in β-Amyloid-Induced Reactive Astrocytes: Potential Rescue from Biomimetic HDLs
title_short Reduced Levels of ABCA1 Transporter Are Responsible for the Cholesterol Efflux Impairment in β-Amyloid-Induced Reactive Astrocytes: Potential Rescue from Biomimetic HDLs
title_sort reduced levels of abca1 transporter are responsible for the cholesterol efflux impairment in β-amyloid-induced reactive astrocytes: potential rescue from biomimetic hdls
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745016/
https://www.ncbi.nlm.nih.gov/pubmed/35008528
http://dx.doi.org/10.3390/ijms23010102
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