Label-free photothermal disruption of cytotoxic aggregates rescues pathology in a C. elegans model of Huntington’s disease

Abstract Aggregation of proteins is a prominent hallmark of virtually all neurodegenerative disorders including Alzheimer’s, Parkinson’s and Huntington’s diseases. Little progress has been made in their treatment to slow or prevent the formation of aggregates by post-translational modification and r...

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Autores principales:	Dmitry A. Nedosekin, TsungYen Chen, Srinivas Ayyadevara, Vladimir P. Zharov, Robert J. Shmookler Reis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/987da26a819c40359aba6ef6a0808345
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spelling	oai:doaj.org-article:987da26a819c40359aba6ef6a08083452021-12-02T18:01:47ZLabel-free photothermal disruption of cytotoxic aggregates rescues pathology in a C. elegans model of Huntington’s disease10.1038/s41598-021-98661-x2045-2322https://doaj.org/article/987da26a819c40359aba6ef6a08083452021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98661-xhttps://doaj.org/toc/2045-2322Abstract Aggregation of proteins is a prominent hallmark of virtually all neurodegenerative disorders including Alzheimer’s, Parkinson’s and Huntington’s diseases. Little progress has been made in their treatment to slow or prevent the formation of aggregates by post-translational modification and regulation of cellular responses to misfolded proteins. Here, we introduce a label-free, laser-based photothermal treatment of polyglutamine (polyQ) aggregates in a C. elegans nematode model of huntingtin-like polyQ aggregation. As a proof of principle, we demonstrated that nanosecond laser pulse-induced local photothermal heating can directly disrupt the aggregates so as to delay their accumulation, maintain motility, and extend the lifespan of treated nematodes. These beneficial effects were validated by confocal photothermal, fluorescence, and video imaging. The results obtained demonstrate that our theranostics platform, integrating photothermal therapy without drugs or other chemicals, combined with advanced imaging to monitor photothermal ablation of aggregates, initiates systemic recovery and thus validates the concept of aggregate-disruption treatments for neurodegenerative diseases in humans.Dmitry A. NedosekinTsungYen ChenSrinivas AyyadevaraVladimir P. ZharovRobert J. Shmookler ReisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dmitry A. Nedosekin TsungYen Chen Srinivas Ayyadevara Vladimir P. Zharov Robert J. Shmookler Reis Label-free photothermal disruption of cytotoxic aggregates rescues pathology in a C. elegans model of Huntington’s disease
description	Abstract Aggregation of proteins is a prominent hallmark of virtually all neurodegenerative disorders including Alzheimer’s, Parkinson’s and Huntington’s diseases. Little progress has been made in their treatment to slow or prevent the formation of aggregates by post-translational modification and regulation of cellular responses to misfolded proteins. Here, we introduce a label-free, laser-based photothermal treatment of polyglutamine (polyQ) aggregates in a C. elegans nematode model of huntingtin-like polyQ aggregation. As a proof of principle, we demonstrated that nanosecond laser pulse-induced local photothermal heating can directly disrupt the aggregates so as to delay their accumulation, maintain motility, and extend the lifespan of treated nematodes. These beneficial effects were validated by confocal photothermal, fluorescence, and video imaging. The results obtained demonstrate that our theranostics platform, integrating photothermal therapy without drugs or other chemicals, combined with advanced imaging to monitor photothermal ablation of aggregates, initiates systemic recovery and thus validates the concept of aggregate-disruption treatments for neurodegenerative diseases in humans.
format	article
author	Dmitry A. Nedosekin TsungYen Chen Srinivas Ayyadevara Vladimir P. Zharov Robert J. Shmookler Reis
author_facet	Dmitry A. Nedosekin TsungYen Chen Srinivas Ayyadevara Vladimir P. Zharov Robert J. Shmookler Reis
author_sort	Dmitry A. Nedosekin
title	Label-free photothermal disruption of cytotoxic aggregates rescues pathology in a C. elegans model of Huntington’s disease
title_short	Label-free photothermal disruption of cytotoxic aggregates rescues pathology in a C. elegans model of Huntington’s disease
title_full	Label-free photothermal disruption of cytotoxic aggregates rescues pathology in a C. elegans model of Huntington’s disease
title_fullStr	Label-free photothermal disruption of cytotoxic aggregates rescues pathology in a C. elegans model of Huntington’s disease
title_full_unstemmed	Label-free photothermal disruption of cytotoxic aggregates rescues pathology in a C. elegans model of Huntington’s disease
title_sort	label-free photothermal disruption of cytotoxic aggregates rescues pathology in a c. elegans model of huntington’s disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/987da26a819c40359aba6ef6a0808345
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Label-free photothermal disruption of cytotoxic aggregates rescues pathology in a C. elegans model of Huntington’s disease

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