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Extracellular vesicle-mediated amyloid transfer to neural progenitor cells: implications for RAGE and HIV infection

Amyloid beta (Aβ) deposition was demonstrated to be elevated in the brains of HIV-infected patients and associated with neurocognitive decline; however, the mechanisms of these processes are poorly understood. The goal of the current study was to address the hypothesis that Aβ can be transferred via...

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Autores principales: András, Ibolya E., Garcia-Contreras, Marta, Yanick, Christopher, Perez, Paola, Sewell, Brice, Durand, Leonardo, Toborek, Michal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027073/
https://www.ncbi.nlm.nih.gov/pubmed/32066471
http://dx.doi.org/10.1186/s13041-020-0562-0
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author András, Ibolya E.
Garcia-Contreras, Marta
Yanick, Christopher
Perez, Paola
Sewell, Brice
Durand, Leonardo
Toborek, Michal
author_facet András, Ibolya E.
Garcia-Contreras, Marta
Yanick, Christopher
Perez, Paola
Sewell, Brice
Durand, Leonardo
Toborek, Michal
author_sort András, Ibolya E.
collection PubMed
description Amyloid beta (Aβ) deposition was demonstrated to be elevated in the brains of HIV-infected patients and associated with neurocognitive decline; however, the mechanisms of these processes are poorly understood. The goal of the current study was to address the hypothesis that Aβ can be transferred via extracellular vesicles (ECVs) from brain endothelial cells to neural progenitor cells (NPCs) and that this process can contribute to abnormal NPC differentiation. Mechanistically, we focused on the role of the receptor for advanced glycation end products (RAGE) and activation of the inflammasome in these events. ECVs loaded with Aβ (Aβ-ECVs) were readily taken up by NPCs and Aβ partly colocalized with the inflammasome markers ASC and NLRP3 in the nuclei of the recipient NPCs. This colocalization was affected by HIV and RAGE inhibition by a high-affinity specific inhibitor FPS-ZM1. Blocking RAGE resulted also in an increase in ECV number produced by brain endothelial cells, decreased Aβ content in ECVs, and diminished Aβ-ECVs transfer to NPC nuclei. Interestingly, both Aβ-ECVs and RAGE inhibition altered NPC differentiation. Overall, these data indicate that RAGE inhibition affects brain endothelial ECV release and Aβ-ECVs transfer to NPCs. These events may modulate ECV-mediated amyloid pathology in the HIV-infected brain and contribute to the development of HIV-associated neurocognitive disorders.
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spelling pubmed-70270732020-02-24 Extracellular vesicle-mediated amyloid transfer to neural progenitor cells: implications for RAGE and HIV infection András, Ibolya E. Garcia-Contreras, Marta Yanick, Christopher Perez, Paola Sewell, Brice Durand, Leonardo Toborek, Michal Mol Brain Research Amyloid beta (Aβ) deposition was demonstrated to be elevated in the brains of HIV-infected patients and associated with neurocognitive decline; however, the mechanisms of these processes are poorly understood. The goal of the current study was to address the hypothesis that Aβ can be transferred via extracellular vesicles (ECVs) from brain endothelial cells to neural progenitor cells (NPCs) and that this process can contribute to abnormal NPC differentiation. Mechanistically, we focused on the role of the receptor for advanced glycation end products (RAGE) and activation of the inflammasome in these events. ECVs loaded with Aβ (Aβ-ECVs) were readily taken up by NPCs and Aβ partly colocalized with the inflammasome markers ASC and NLRP3 in the nuclei of the recipient NPCs. This colocalization was affected by HIV and RAGE inhibition by a high-affinity specific inhibitor FPS-ZM1. Blocking RAGE resulted also in an increase in ECV number produced by brain endothelial cells, decreased Aβ content in ECVs, and diminished Aβ-ECVs transfer to NPC nuclei. Interestingly, both Aβ-ECVs and RAGE inhibition altered NPC differentiation. Overall, these data indicate that RAGE inhibition affects brain endothelial ECV release and Aβ-ECVs transfer to NPCs. These events may modulate ECV-mediated amyloid pathology in the HIV-infected brain and contribute to the development of HIV-associated neurocognitive disorders. BioMed Central 2020-02-17 /pmc/articles/PMC7027073/ /pubmed/32066471 http://dx.doi.org/10.1186/s13041-020-0562-0 Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
András, Ibolya E.
Garcia-Contreras, Marta
Yanick, Christopher
Perez, Paola
Sewell, Brice
Durand, Leonardo
Toborek, Michal
Extracellular vesicle-mediated amyloid transfer to neural progenitor cells: implications for RAGE and HIV infection
title Extracellular vesicle-mediated amyloid transfer to neural progenitor cells: implications for RAGE and HIV infection
title_full Extracellular vesicle-mediated amyloid transfer to neural progenitor cells: implications for RAGE and HIV infection
title_fullStr Extracellular vesicle-mediated amyloid transfer to neural progenitor cells: implications for RAGE and HIV infection
title_full_unstemmed Extracellular vesicle-mediated amyloid transfer to neural progenitor cells: implications for RAGE and HIV infection
title_short Extracellular vesicle-mediated amyloid transfer to neural progenitor cells: implications for RAGE and HIV infection
title_sort extracellular vesicle-mediated amyloid transfer to neural progenitor cells: implications for rage and hiv infection
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027073/
https://www.ncbi.nlm.nih.gov/pubmed/32066471
http://dx.doi.org/10.1186/s13041-020-0562-0
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