Sánchez-Porras Valentina, Guevara-Morales Johana Maria, Echeverri-Peña Olga Yaneth
Instituto de Errores Innatos del Metabolismo, Facultad de Ciencias, Pontificia Universidad Javeriana, Carrera 7 # 43-82, Ed. 54, Lab 303A, Bogotá 110231, Colombia.
Int J Mol Sci. 2023 Aug 5;24(15):12481. doi: 10.3390/ijms241512481.
Pompe disease (PD) is caused by mutations in the gene, which encodes the lysosomal enzyme acid alpha-glucosidase, causing lysosomal glycogen accumulation, mainly in muscular tissue. Autophagic buildup is considered the main factor affecting skeletal muscle, although other processes are also involved. Uncovering how these mechanisms are interconnected could be an approximation to address long-lasting concerns, like the differential skeletal and cardiac involvement in each clinical phenotype. In this sense, a network reconstruction based on a comprehensive literature review of evidence found in PD enriched with the STRING database and other scientific articles is presented. The role of autophagic lysosome reformation, PGC-1α, MCOLN1, calcineurin, and Keap1 as intermediates between the events involved in the pathologic cascade is discussed and contextualized within their relationship with mTORC1/AMPK. The intermediates and mechanisms found open the possibility of new hypotheses and questions that can be addressed in future experimental studies of PD.
庞贝病（PD）由编码溶酶体酶酸性α-葡萄糖苷酶的基因突变引起，导致溶酶体糖原积累，主要发生在肌肉组织中。自噬积累被认为是影响骨骼肌的主要因素，尽管其他过程也参与其中。揭示这些机制如何相互关联可能有助于解决长期存在的问题，比如每种临床表型中骨骼和心脏受累情况的差异。从这个意义上讲，本文基于对庞贝病相关证据的全面文献综述，并结合STRING数据库及其他科学文章进行了网络重建。文中讨论了自噬溶酶体再形成、PGC-1α、MCOLN1、钙调神经磷酸酶和Keap1作为病理级联反应相关事件之间中间体的作用，并将其置于与mTORC1/AMPK的关系中进行背景分析。所发现的中间体和机制为未来庞贝病实验研究中可能探讨的新假说和新问题提供了可能性。
