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Reactivation of autophagy by spermidine ameliorates the myopathic defects of collagen VI-null mice

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 demo...

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Autores principales: Chrisam, Martina, Pirozzi, Marinella, Castagnaro, Silvia, Blaauw, Bert, Polishchuck, Roman, Cecconi, Francesco, Grumati, Paolo, Bonaldo, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835186/
https://www.ncbi.nlm.nih.gov/pubmed/26565691
http://dx.doi.org/10.1080/15548627.2015.1108508
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author Chrisam, Martina
Pirozzi, Marinella
Castagnaro, Silvia
Blaauw, Bert
Polishchuck, Roman
Cecconi, Francesco
Grumati, Paolo
Bonaldo, Paolo
author_facet Chrisam, Martina
Pirozzi, Marinella
Castagnaro, Silvia
Blaauw, Bert
Polishchuck, Roman
Cecconi, Francesco
Grumati, Paolo
Bonaldo, Paolo
author_sort Chrisam, Martina
collection PubMed
description 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.
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spelling pubmed-48351862016-04-29 Reactivation of autophagy by spermidine ameliorates the myopathic defects of collagen VI-null mice Chrisam, Martina Pirozzi, Marinella Castagnaro, Silvia Blaauw, Bert Polishchuck, Roman Cecconi, Francesco Grumati, Paolo Bonaldo, Paolo Autophagy Basic Brief Report 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. Taylor & Francis 2015-11-13 /pmc/articles/PMC4835186/ /pubmed/26565691 http://dx.doi.org/10.1080/15548627.2015.1108508 Text en © 2015 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
spellingShingle Basic Brief Report
Chrisam, Martina
Pirozzi, Marinella
Castagnaro, Silvia
Blaauw, Bert
Polishchuck, Roman
Cecconi, Francesco
Grumati, Paolo
Bonaldo, Paolo
Reactivation of autophagy by spermidine ameliorates the myopathic defects of collagen VI-null mice
title Reactivation of autophagy by spermidine ameliorates the myopathic defects of collagen VI-null mice
title_full Reactivation of autophagy by spermidine ameliorates the myopathic defects of collagen VI-null mice
title_fullStr Reactivation of autophagy by spermidine ameliorates the myopathic defects of collagen VI-null mice
title_full_unstemmed Reactivation of autophagy by spermidine ameliorates the myopathic defects of collagen VI-null mice
title_short Reactivation of autophagy by spermidine ameliorates the myopathic defects of collagen VI-null mice
title_sort reactivation of autophagy by spermidine ameliorates the myopathic defects of collagen vi-null mice
topic Basic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835186/
https://www.ncbi.nlm.nih.gov/pubmed/26565691
http://dx.doi.org/10.1080/15548627.2015.1108508
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