Journal
SCIENTIFIC REPORTS
Volume 11, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41598-021-98661-x
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Funding
- U.S. Veterans Administration [IO1 BX001655, IK6 BX004851]
- NIH [P01-AG012411-17, R01 AG062254-01]
- NSF [DBI-0852737]
- UAMS College of Medicine Honors in Research program
- Arkansas Claude Pepper Center (NIH) [P30 AG028718]
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The study introduces a laser-based photothermal treatment method for aggregates, which successfully delays their accumulation and enhances the lifespan of treated nematodes. This drug-free therapy, combining photothermal treatment with advanced imaging techniques, effectively disrupts aggregates and initiates systemic recovery, validating the concept of aggregate-disruption treatments for neurodegenerative diseases in humans.
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.
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