title: Investigating heart-specific toxicity of amyloidogenic immunoglobulin light chains: A lesson from C. elegans.
abstract: Abnormalities in protein folding are involved in many localized and systemic diseases, all of which are characterized by insoluble amyloid formation and deposition. In immunoglobulin light chain (LC) amyloidosis, the most frequent systemic form of amyloidosis, the amyloid involvement of the heart dictates the prognosis and the elucidation of the mechanism of heart targeting and toxicity is essential for designing and testing new effective treatments. To this end, the availability of an appropriate animal model is crucial. We recently described the use of C. elegans as an innovative experimental system to investigate in vivo the pathogenic effects of monoclonal LC. This idea stems from the knowledge that the worm's pharynx is an "ancestral heart" with the additional ability to recognize stressor compounds. The feeding of worms with LC purified from patients suffering from cardiomyopathy, selectively and permanently impaired the pharyngeal function. This irreversible damage resulted in time, in a significant reduction in the lifespan of worms. We also reported that the ability of LC to generate reactive oxygen species was associated with their toxic effects and was counteracted by anti-oxidant compounds. This new nematode-based assay represents a promising model for elucidating the heart-specific toxicity of LC and for a rapid screening of new therapeutic strategies.
authors.affiliation: Department of Molecular Biochemistry and Pharmacology; IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" ; Milan, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Diomede
authors.affiliation: Amyloid Research and Treatment Center; Foundation IRCCS Policlinico San Matteo ; Pavia, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Rognoni
authors.affiliation: Amyloid Research and Treatment Center; Foundation IRCCS Policlinico San Matteo ; Pavia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lavatelli
authors.affiliation: Department of Molecular Biochemistry and Pharmacology; IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" ; Milan, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Romeo
authors.affiliation: Amyloid Research and Treatment Center; Foundation IRCCS Policlinico San Matteo ; Pavia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: di Fonzo
authors.affiliation: Bio-imaging Unit, Department of Cardiovascular Research; IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" ; Milano, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Foray
authors.affiliation: Bio-imaging Unit, Department of Cardiovascular Research; IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" ; Milano, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Fiordaliso
authors.affiliation: Amyloid Research and Treatment Center; Foundation IRCCS Policlinico San Matteo ; Pavia, Italy ; Department of Molecular Medicine; University of Pavia ; Pavia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Palladini
authors.affiliation: Amyloid Research and Treatment Center; Foundation IRCCS Policlinico San Matteo ; Pavia, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Valentini
authors.affiliation: Medical Oncology Unit; Foundation IRCCS Policlinico San Matteo ; Pavia, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Perfetti
authors.affiliation: Department of Molecular Biochemistry and Pharmacology; IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" ; Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Salmona
authors.affiliation: Amyloid Research and Treatment Center; Foundation IRCCS Policlinico San Matteo ; Pavia, Italy ; Department of Molecular Medicine; University of Pavia ; Pavia, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Merlini
keywords: C. elegans; amyloidosis; cardiotoxicity; immunoglobulin light chains; pharynx