Enhanced inhibition of amyloid formation by heat shock protein 90 immobilized on nanoparticles

As the population ages, an epidemic of neurodegenerative diseases with devastating social consequences is looming. To address the pathologies leading to amyloid-related dementia, novel therapeutic strategies must be developed for the treatment or prevention of neural protein-folding disorders. Nanot...

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Autores: Rodríguez Ramos, Ana, González, Jesús A., López Fanarraga, Mónica|||0000-0003-4754-311X
Formato: artículo
Fecha de publicación:2023
País:España
Recursos:Universidad de Cantabria (UC)
Repositorio:UCrea Repositorio Abierto de la Universidad de Cantabria
Idioma:inglés
OAI Identifier:oai:repositorio.unican.es:10902/29871
Acesso em linha:https://hdl.handle.net/10902/29871
Access Level:acceso abierto
Palavra-chave:Molecular chaperone
Protein renaturation
Amyloid
Neurodegeneration
Nanorobot
Microrobot
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spelling Enhanced inhibition of amyloid formation by heat shock protein 90 immobilized on nanoparticlesRodríguez Ramos, AnaGonzález, Jesús A.López Fanarraga, Mónica|||0000-0003-4754-311XMolecular chaperoneProtein renaturationAmyloidNeurodegenerationNanorobotMicrorobotAs the population ages, an epidemic of neurodegenerative diseases with devastating social consequences is looming. To address the pathologies leading to amyloid-related dementia, novel therapeutic strategies must be developed for the treatment or prevention of neural protein-folding disorders. Nanotechnology will be crucial to this scenario, especially in the design of nanoscale systems carrying therapeutic compounds that can navigate the nervous system and identify amyloid to treat it in situ. In this line, we have recently designed a highly simplified and versatile nanorobot consisting of a protein coating based on the heat shock protein 90 (Hsp90) chaperone that not only propels nanoparticles using ATP but also endows them with the extraordinary ability to fold and restore the activity of heat-denatured proteins. Here, we assess the effectiveness of these nanosystems in inhibiting/reducing the aggregation of amyloidogenic proteins. Using Raman spectroscopy, we qualitatively and quantitatively analyze amyloid by identifying and semi-quantifying the Amide I band. Our findings indicate that the coupling of Hsp90 to nanoparticles results in a more potent inhibition of amyloid formation when compared to the soluble protein. We propose that this enhanced performance may be attributed to enhanced release-capture cycles of amyloid precursor oligomers by Hsp90 molecules nearby on the nanosurface. Intelligent biocompatible coatings, like the one described here, that enhance the diffusivity and self-propulsion of nanoparticles while enabling them to carry out critical functions such as environmental scanning, identification, and amyloid prevention, present an exceptional opportunity for the development of advanced nanodevices in biomedical applications. This approach, which combined active biomolecules with synthetic materials, is poised to reveal remarkable prospects in the field of nanomedicine and biotechnology.ACKNOWLEDGMENTS: The authors acknowledge the financial support from the Spanish Instituto de Salud Carlos iii co-funded by the European Regional Development Fund, “Investing in your future” under projects ref. PI22/00030 and PI19/00349, and grant TED2021-129248B-I00 funded by MCIN/AEI/ 10.13039/501100011033 and by the “European Union NextGeneration EU/PRTR”. We also thank the Gobierno Regional de Cantabria and IDIVAL for the project refs IDI 20/22, INNVAL 21/19, and PREVAL 19/04 fellowship to A.R.R. and technological and administrative services. We are grateful to Dr. L García-Hevia for reading the manuscript.American Chemical SocietyUniversidad de Cantabria20232023-01-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttps://hdl.handle.net/10902/29871ACS Chemical Neuroscience, 2023, 14, 2811-2817reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/298712026-06-02T12:39:31Z
dc.title.none.fl_str_mv Enhanced inhibition of amyloid formation by heat shock protein 90 immobilized on nanoparticles
title Enhanced inhibition of amyloid formation by heat shock protein 90 immobilized on nanoparticles
spellingShingle Enhanced inhibition of amyloid formation by heat shock protein 90 immobilized on nanoparticles
Rodríguez Ramos, Ana
Molecular chaperone
Protein renaturation
Amyloid
Neurodegeneration
Nanorobot
Microrobot
title_short Enhanced inhibition of amyloid formation by heat shock protein 90 immobilized on nanoparticles
title_full Enhanced inhibition of amyloid formation by heat shock protein 90 immobilized on nanoparticles
title_fullStr Enhanced inhibition of amyloid formation by heat shock protein 90 immobilized on nanoparticles
title_full_unstemmed Enhanced inhibition of amyloid formation by heat shock protein 90 immobilized on nanoparticles
title_sort Enhanced inhibition of amyloid formation by heat shock protein 90 immobilized on nanoparticles
dc.creator.none.fl_str_mv Rodríguez Ramos, Ana
González, Jesús A.
López Fanarraga, Mónica|||0000-0003-4754-311X
author Rodríguez Ramos, Ana
author_facet Rodríguez Ramos, Ana
González, Jesús A.
López Fanarraga, Mónica|||0000-0003-4754-311X
author_role author
author2 González, Jesús A.
López Fanarraga, Mónica|||0000-0003-4754-311X
author2_role author
author
dc.contributor.none.fl_str_mv Universidad de Cantabria
dc.subject.none.fl_str_mv Molecular chaperone
Protein renaturation
Amyloid
Neurodegeneration
Nanorobot
Microrobot
topic Molecular chaperone
Protein renaturation
Amyloid
Neurodegeneration
Nanorobot
Microrobot
description As the population ages, an epidemic of neurodegenerative diseases with devastating social consequences is looming. To address the pathologies leading to amyloid-related dementia, novel therapeutic strategies must be developed for the treatment or prevention of neural protein-folding disorders. Nanotechnology will be crucial to this scenario, especially in the design of nanoscale systems carrying therapeutic compounds that can navigate the nervous system and identify amyloid to treat it in situ. In this line, we have recently designed a highly simplified and versatile nanorobot consisting of a protein coating based on the heat shock protein 90 (Hsp90) chaperone that not only propels nanoparticles using ATP but also endows them with the extraordinary ability to fold and restore the activity of heat-denatured proteins. Here, we assess the effectiveness of these nanosystems in inhibiting/reducing the aggregation of amyloidogenic proteins. Using Raman spectroscopy, we qualitatively and quantitatively analyze amyloid by identifying and semi-quantifying the Amide I band. Our findings indicate that the coupling of Hsp90 to nanoparticles results in a more potent inhibition of amyloid formation when compared to the soluble protein. We propose that this enhanced performance may be attributed to enhanced release-capture cycles of amyloid precursor oligomers by Hsp90 molecules nearby on the nanosurface. Intelligent biocompatible coatings, like the one described here, that enhance the diffusivity and self-propulsion of nanoparticles while enabling them to carry out critical functions such as environmental scanning, identification, and amyloid prevention, present an exceptional opportunity for the development of advanced nanodevices in biomedical applications. This approach, which combined active biomolecules with synthetic materials, is poised to reveal remarkable prospects in the field of nanomedicine and biotechnology.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10902/29871
url https://hdl.handle.net/10902/29871
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv ACS Chemical Neuroscience, 2023, 14, 2811-2817
reponame:UCrea Repositorio Abierto de la Universidad de Cantabria
instname:Universidad de Cantabria (UC)
instname_str Universidad de Cantabria (UC)
reponame_str UCrea Repositorio Abierto de la Universidad de Cantabria
collection UCrea Repositorio Abierto de la Universidad de Cantabria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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