title: Drosophila as a potential model to ameliorate mutant Huntington-mediated cardiac amyloidosis.
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.
authors.affiliation: Department 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.
authors.forename: Adriana S
authors.initials: AS
authors.lastname: Trujillo
authors.affiliation: Department of Biology; Molecular Biology and Heart Institutes; San Diego State University ; San Diego, CA USA.
authors.forename: Raul
authors.initials: R
authors.lastname: Ramos
authors.affiliation: Development and Aging Program; Sanford-Burnham Institute for Medical Research ; La Jolla, CA USA.
authors.forename: Rolf
authors.initials: R
authors.lastname: Bodmer
authors.affiliation: Department of Biology; Molecular Biology and Heart Institutes; San Diego State University ; San Diego, CA USA.
authors.forename: Sanford I
authors.initials: SI
authors.lastname: Bernstein
authors.affiliation: Development and Aging Program; Sanford-Burnham Institute for Medical Research ; La Jolla, CA USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Ocorr
authors.affiliation: Department 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.
authors.forename: Girish C
authors.initials: GC
authors.lastname: Melkani
keywords: Drosophila melanogaster; Huntington's disease; cardiac amyloidosis; oxidative stress; protein misfolding