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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

Sierri, Giulia, Dal Magro, Roberta, Vergani, Barbara, Leone, Biagio Eugenio, Formicola, Beatrice, Taiarol, Lorenzo, Fagioli, Stefano, Kravicz, Marcelo, Tremolizzo, Lucio, Calabresi, Laura, Re, Francesca·2021·International Journal of Molecular Sciences

Abstract

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 Aβ1-42-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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Metadata

Authors
Sierri, G., Dal Magro, R., Vergani, B., Leone, B. E., Formicola, B., Taiarol, L., Fagioli, S., Kravicz, M., Tremolizzo, L., Calabresi, L., & Re, F.
Affiliations
  • BioNanoMedicine Center NANOMIB, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
  • School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
  • Department of Pharmacological and Biomolecular Science, Centro Grossi Paoletti, University of Milan, 20133 Milan, Italy
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2021-12-22
Volume
23
Issue
1
Pages
102
ISSN
1422-0067
Cited by
16
References
2
Language
en
Funders
PRIN Research Italy (2017PFYK27)

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