RESUMO
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.
Assuntos
Doença de Huntington/etiologia , Doença de Huntington/metabolismo , Agregados Proteicos/efeitos da radiação , Agregação Patológica de Proteínas/metabolismo , Animais , Caenorhabditis elegans , Modelos Animais de Doenças , Humanos , Doença de Huntington/patologia , Doença de Huntington/terapia , Lasers , Terapia com Luz de Baixa Intensidade , Peptídeos/metabolismo , Terapia Fototérmica , Agregação Patológica de Proteínas/terapia , Proteínas Recombinantes de Fusão/metabolismoRESUMO
The studies of microbes have been instrumental in combatting infectious diseases, but they have also led to great insights into basic biological mechanism like DNA replication, transcription, and translation of mRNA. In particular, the studies of bacterial viruses, also called bacteriophage, have been quite useful to study specific cellular processes because of the ease to isolate their DNA, mRNA, and proteins. Here, I review the recent discovery of how properties of the filamentous phage M13 emerge as a novel approach to combat neurodegenerative diseases.