Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.



Diphenyl diselenide protects a Caenorhabditis elegans model for Huntington's disease by activation of the antioxidant pathway and a decrease in protein aggregation

Author affiliations

Abstract

Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disease with a distinct phenotype. It occurs due to a mutation in the huntingtin (or IT19) gene with an abnormal CAG repeat, leading to a variable length N-terminal polyglutamine chain (poly-Q). Like most neurodegenerative diseases, HD is characterized by the abnormal deposition and aggregation of proteins in the cell, which impairs the proteostasis and disrupts cellular homeostasis. In this study, we used Caenorhabditis elegans as an animal model due to its easy genetic manipulation and high homology of genes and signaling pathways with mammals. Worms were exposed to diphenyl diselenide (PhSe)2 at 25, 50 and 100 μM, and then we analyzed the polyQ aggregation, neurodegeneration, touch response, reactive oxygen species (ROS) levels, lifespan and health span. In addition, we analyzed the involvement of the transcription factor DAF-16, a FOXO-ortholog, and the downstream heat-shock protein-16.2 (HSP-16.2) and superoxide dismutase-3 (SOD-3). Our data demonstrate that chronic treatment with (PhSe)2 reduced polyQ aggregation in muscle and polyQ mediated neuronal cell death of sensory neurons ASH, as well as maintaining the neuronal function. In addition, (PhSe)2 decreased ROS levels and extended the lifespan and health span of wild type and PolyQ mutant worms. The mechanism proposed is the activation of DAF-16, HSP-16.2 and SOD-3 in whole body tissues to increase the antioxidant capacity and regulation of proteostasis, decreasing PolyQ aggregation and toxicity and reducing ROS levels, leading to an increase in lifespan, and healthspan. Our findings provide new clues for treatment strategies for neurodegenerative diseases and other diseases caused by age-related protein aggregation.

Graphical abstract: Diphenyl diselenide protects a Caenorhabditis elegans model for Huntington's disease by activation of the antioxidant pathway and a decrease in protein aggregation

Back to tab navigation

Article information


Submitted
21 Mar 2020
Accepted
05 May 2020
First published
05 May 2020

Metallomics, 2020, Advance Article
Article type
Paper

Diphenyl diselenide protects a Caenorhabditis elegans model for Huntington's disease by activation of the antioxidant pathway and a decrease in protein aggregation

F. Bicca Obetine Baptista, L. P. Arantes, M. L. Machado, A. F. da Silva, L. Marafiga Cordeiro, T. L. da Silveira and F. A. A. Soares, Metallomics, 2020, Advance Article , DOI: 10.1039/D0MT00074D

Social activity

Search articles by author

Spotlight

Advertisements