Pompe disease (PD) is an autosomal recessive muscular disorder caused by deficiency of the glycogen hydrolytic enzyme acid α-glucosidase (GAA). The enzyme replacement therapy, currently the only available therapy for PD patients, is efficacious in improving cardiomyopathy in the infantile form, but not equally effective in the late onset cases with involvement of skeletal muscle. Correction of the skeletal muscle phenotype has indeed been challenging, probably due to concomitant dysfunctional autophagy. The increasing attention to the pathogenic mechanisms of PD and the search of new therapeutic strategies prompted us to generate and characterize a novel transient PD model, using zebrafish. Our model presented increased glycogen content, markedly altered motor behavior and increased lysosome content, in addition to altered expression of the autophagy-related transcripts and proteins Beclin1, p62 and Lc3b. Furthermore, the model was used to assess the beneficial effects of 3-bromopyruvic acid (3-BrPA). Treatment with 3-BrPA induced amelioration of the model phenotypes regarding glycogen storage, motility behavior and autophagy-related transcripts and proteins. Our zebrafish PD model recapitulates most of the defects observed in human patients, proving to be a powerful translational model. Moreover, 3-BrPA unveiled to be a promising compound for treatment of conditions with glycogen accumulation.

中文翻译：

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斑马鱼庞贝病模型中的糖原存储量通过3-BrPA处理得以减少。

庞贝病（PD）是由糖原水解酶酸性α-葡萄糖苷酶（GAA）缺乏引起的常染色体隐性遗传性肌肉疾病。酶替代疗法是目前PD患者唯一可用的疗法，可有效改善婴儿型心肌病，但在骨骼肌受累的迟发性病例中效果不佳。骨骼肌表型的校正确实具有挑战性，可能是由于自噬功能障碍引起的。对PD致病机制的日益关注以及对新治疗策略的探索促使我们使用斑马鱼来生成和表征新型瞬时PD模型。我们的模型显示糖原含量增加，运动行为明显改变，溶酶体含量增加，除了改变自噬相关转录本和蛋白Beclin1，p62和Lc3b的表达。此外，该模型用于评估3-溴丙酮酸（3-BrPA）的有益作用。3-BrPA处理可改善模型表型的糖原贮积，运动行为以及自噬相关转录本和蛋白质。我们的斑马鱼PD模型概括了人类患者中观察到的大多数缺陷，被证明是功能强大的翻译模型。此外，3-BrPA被公认为是一种治疗糖原积累症的有前途的化合物。运动行为和自噬相关的转录本和蛋白质。我们的斑马鱼PD模型概括了人类患者中观察到的大多数缺陷，被证明是功能强大的翻译模型。此外，3-BrPA被公认为是一种治疗糖原积累症的有前途的化合物。运动行为和自噬相关的转录本和蛋白质。我们的斑马鱼PD模型概括了人类患者中观察到的大多数缺陷，被证明是功能强大的翻译模型。此外，3-BrPA被公认为是一种治疗糖原积累症的有前途的化合物。