title: Reactivation of autophagy by spermidine ameliorates the myopathic defects of collagen VI-null mice.
abstract: Autophagy is a self-degradative process responsible for the clearance of damaged or unnecessary cellular components. We have previously found that persistence of dysfunctional organelles due to autophagy failure is a key event in the pathogenesis of COL6/collagen VI-related myopathies, and have demonstrated that reactivation of a proper autophagic flux rescues the muscle defects of Col6a1-null (col6a1(-/-)) mice. Here we show that treatment with spermidine, a naturally occurring nontoxic autophagy inducer, is beneficial for col6a1(-/-) mice. Systemic administration of spermidine in col6a1(-/-) mice reactivated autophagy in a dose-dependent manner, leading to a concurrent amelioration of the histological and ultrastructural muscle defects. The beneficial effects of spermidine, together with its being easy to administer and the lack of overt side effects, open the field for the design of novel nutraceutical strategies for the treatment of muscle diseases characterized by autophagy impairment.
authors.affiliation: a Department of Molecular Medicine ; University of Padova ; Padova , Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Chrisam
authors.affiliation: b Telethon Institute of Genetic and Medicine (TIGEM) ; Napoli , Italy.
authors.forename: Marinella
authors.initials: M
authors.lastname: Pirozzi
authors.affiliation: a Department of Molecular Medicine ; University of Padova ; Padova , Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Castagnaro
authors.affiliation: c Venetian Institute of Molecular Medicine (VIMM) ; Padova , Italy.
authors.forename: Bert
authors.initials: B
authors.lastname: Blaauw
authors.affiliation: b Telethon Institute of Genetic and Medicine (TIGEM) ; Napoli , Italy.
authors.forename: Roman
authors.initials: R
authors.lastname: Polishchuck
authors.affiliation: d IRCCS Fondazione Santa Lucia ; Rome , Italy.|e Department of Biology ; University of Rome Tor Vergata ; Rome , Italy.|f Danish Cancer Society Research Center ; Copenhagen , Denmark.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cecconi
authors.affiliation: a Department of Molecular Medicine ; University of Padova ; Padova , Italy.|g Institute of Biochemistry II ; Goethe University ; Frankfurt am Main , Germany.
authors.forename: Paolo
authors.initials: P
authors.lastname: Grumati
authors.affiliation: a Department of Molecular Medicine ; University of Padova ; Padova , Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bonaldo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001343:Autophagy / Q000235:genetics* / Q000502:physiology; D024142:Collagen Type VI / Q000172:deficiency*; D004195:Disease Models, Animal; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000473:pathology; D009132:Muscles / Q000378:metabolism* / Q000473:pathology; D009135:Muscular Diseases / Q000473:pathology*; D013095:Spermidine / Q000378:metabolism*
chemical_list: D024142:Collagen Type VI; D013095:Spermidine
keywords: autophagy; collagen VI; muscular dystrophies; skeletal muscle; spermidine