Reactivation of autophagy by spermidine ameliorates the myopathic defects of collagen VI-null mice.
Reactivation of autophagy by spermidine ameliorates the myopathic defects of collagen VI-null mice.
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DOI：
10.1080/15548627.2015.1108508
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发表时间：
2015
期刊：
影响因子：
13.3
通讯作者：
Bonaldo P
中科院分区：
文献类型：
--
作者：
Chrisam M;Pirozzi M;Castagnaro S;Blaauw B;Polishchuck R;Cecconi F;Grumati P;Bonaldo P
自噬是一种自我降解过程，负责清除受损或不必要的细胞成分。我们先前已经发现，由于自噬失败而导致的功能失调的细胞器的持续存在是COL 6/胶原VI相关肌病发病机制中的关键事件，并且已经证明了适当自噬通量的重新激活可以挽救Col 6a 1-null（col 6a 1 −/−）小鼠的肌肉缺陷。在这里，我们表明，亚精胺，一种天然存在的无毒自噬诱导剂，治疗对col 6a 1 −/−小鼠有益。在col 6a 1 −/−小鼠中，亚精胺的全身给药以剂量依赖性方式重新激活自噬，导致组织学和超微结构肌肉缺陷的同时改善。亚精胺的有益效果，连同其易于管理和缺乏明显的副作用，为设计用于治疗以自噬损伤为特征的肌肉疾病的新型营养药物策略打开了领域。
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.