PDF(Pubmed)
Abstract：
Ryanodine receptors (RyR) are intracellular calcium (Ca2+) release channels on the sarcoplasmic reticulum of skeletal and cardiac muscles that play a central role in excitation-contraction coupling. Genetic mutations or posttranslational modifications of RyR causes hyperactivation of the channel, leading to various skeletal muscle and heart diseases. Currently, no specific treatments exist for most RyR-associated diseases. Recently, high-throughput screening (HTS) assays have been developed to identify potential candidates for treating RyR-related muscle diseases. These assays have successfully identified several compounds as novel RyR inhibitors, which are effective in animal models. In this review, we will focus on recent progress in HTS assays and discuss future perspectives of these promising approaches.
摘要：
Ryanodine受体（RyR）是骨骼肌和心肌肌浆网上的细胞内钙（Ca2）释放通道，在兴奋-收缩偶联中起着核心作用。RyR的基因突变或翻译后修饰会导致通道过度激活，导致各种骨骼肌和心脏疾病。目前,大多数RyR相关疾病没有特异性治疗方法。最近,已经开发了高通量筛选(HTS)测定法来鉴定治疗RyR相关肌肉疾病的潜在候选物。这些试验已经成功地鉴定了几种化合物作为新型RyR抑制剂，在动物模型中是有效的。在这次审查中,我们将重点介绍HTS检测的最新进展，并讨论这些有前途的方法的未来前景。
