Research Projects to Clarify the Molecular Pathogenesis and to Develop Therapeutic or Preventive Strategy for Cardiomyopathy

在这项研究中，我们已经确定CARP突变是心肌病的分子基础。我们还发现了PGM1作为ZASP的结合伴侣，并揭示了DCM相关的ZASP突变损害了与PGM1的结合。此外，发现心肌细胞代谢应激时，PGM1定位于Z盘。另一方面，我们发现M21增强了M110的磷酸化。最后，我们证明了钙增敏剂可以预防扩张型心肌病模型小鼠心脏的病理变化。

In this research, we have identified CARP mutations as the molecular basis of cardiomyopathy. We also found PGM1 as a binding partner of ZASP and revealed that DCM-associated ZASP mutations impaired the binding to PGM1. In addition, PGM1 was found to be localized to Z-disc upon metabolic stress of cardiomyocytes. On the other hand, we reveled that M21 enhanced the phosphorylation of M110. Finally, we demonstrated that calcium sensitizer could prevent the pathological changes in the hearts of a model mice for dilated cardiomyopathy.