肌节
医学
肌球蛋白
心肌病
MYH6
扩张型心肌病
MYH7
提丁
肥厚性心肌病
心脏病学
生物信息学
内科学
心力衰竭
细胞生物学
心肌细胞
肌球蛋白轻链激酶
生物
作者
Sarah Lehman,Claudia Crocini,Leslie A. Leinwand
标识
DOI:10.1038/s41569-022-00682-0
摘要
Variants in >12 genes encoding sarcomeric proteins can cause various cardiomyopathies. The two most common are hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Current therapeutics do not target the root causes of these diseases, but attempt to prevent disease progression and/or to manage symptoms. Accordingly, novel approaches are being developed to treat the cardiac muscle dysfunction directly. Challenges to developing therapeutics for these diseases include the diverse mechanisms of pathogenesis, some of which are still being debated and defined. Four small molecules that modulate the myosin motor protein in the cardiac sarcomere have shown great promise in the settings of HCM and DCM, regardless of the underlying genetic pathogenesis, and similar approaches are being developed to target other components of the sarcomere. In the setting of HCM, mavacamten and aficamten bind to the myosin motor and decrease the ATPase activity of myosin. In the setting of DCM, omecamtiv mecarbil and danicamtiv increase myosin activity in cardiac muscle (but omecamtiv mecarbil decreases myosin activity in vitro). In this Review, we discuss the therapeutic strategies to alter sarcomere contractile activity and summarize the data indicating that targeting one protein in the sarcomere can be effective in treating patients with genetic variants in other sarcomeric proteins, as well as in patients with non-sarcomere-based disease. Variants in genes encoding sarcomeric proteins can cause hypertrophic or dilated cardiomyopathy. In this Review, the authors discuss therapeutic strategies to target the cardiac sarcomere, focusing on four small molecules that have been developed that inhibit or activate the myosin motor protein to decrease or increase contractile force, respectively.
科研通智能强力驱动
Strongly Powered by AbleSci AI