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Updated: Mar 24, 2026
Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster
Published on: March 12, 2018
Drosophila as a potential model to ameliorate mutant Huntington-mediated cardiac amyloidosis
Adriana S Trujillo1, Raul Ramos2, Rolf Bodmer3
1Department of Biology; Molecular Biology and Heart Institutes; San Diego State University; San Diego, CA USA; Development and Aging Program; Sanford-Burnham Institute for Medical Research; La Jolla, CA USA.
Insights
Huntington's disease (HD) cardiac amyloidosis was modeled in Drosophila, revealing oxidative stress and myofibrillar defects. Genetic strategies targeting folding and oxidative stress pathways successfully suppressed this cardiomyopathy, offering insights into polyglutamine expansion disorders.
Area of Science:
- Cardiovascular Biology
- Neurodegenerative Diseases
- Genetics and Genomics
Background:
- Huntington's disease (HD) is linked to amyloid protein aggregation.
- Cardiac disease is a significant cause of mortality in HD patients.
- The mechanisms underlying HD-induced cardiomyopathy are not well understood.
Purpose of the Study:
- To establish a Drosophila heart model for studying mutant HD-induced cardiomyopathy.
- To investigate the role of amyloid aggregates and oxidative stress in HD cardiac dysfunction.
- To identify potential therapeutic targets for suppressing HD cardiac amyloidosis.
Main Methods:
- Expression of HD-causing PolyQ in Drosophila cardiomyocytes.
- Utilizing Drosophila genetic techniques to modulate relevant pathways.
- Assessing myofibrillar organization, oxidative stress, and physiological defects.
Main Results:
- The Drosophila model recapitulated amyloid aggregate-induced oxidative stress and myofibrillar disorganization.
- Expression of mutant PolyQ in cardiomyocytes led to physiological cardiac defects.
- Modulating folding and oxidative stress pathways suppressed the observed cardiomyopathy.
Conclusions:
- Drosophila serves as a viable model for studying HD cardiac amyloidosis.
- Oxidative stress and protein folding defects are key contributors to HD cardiomyopathy.
- Genetic suppression strategies show promise for treating cardiac complications in polyglutamine expansion disorders.
Abstract:
Several human diseases, including Huntington's disease (HD), are associated with the expression of mutated, misfolded, and aggregation-prone amyloid proteins. Cardiac disease is the second leading cause of death in HD, which has been mainly studied as a neurodegenerative disease that is caused by expanded polyglutamine repeats in the huntingtin protein. Since the mechanistic basis of mutant HD-induced cardiomyopathy is unknown, we established a Drosophila heart model that exhibited amyloid aggregate-induced oxidative stress, resulting in myofibrillar disorganization and physiological defects upon expression of HD-causing PolyQ expression in cardiomyocytes. Using powerful Drosophila genetic techniques, we suppressed mutant HD-induced cardiomyopathy by modulating pathways associated with folding defects and oxidative stress. In this addendum, we describe additional potential molecular players that might be associated with HD cardiac amyloidosis. Drosophila, with its high degree of conservation to the human genome and many techniques to manipulate its gene expression, will be an excellent model for the suppression of cardiac amyloidosis linked to other polyglutamine expansion repeat disorders.
