Thorkelsson Andres, Chin Michael T
Tufts University School of Medicine, Tufts University, Boston, MA 02111, USA.
Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
Int J Mol Sci. 2024 Feb 29;25(5):2826. doi: 10.3390/ijms25052826.
Alpha-B-crystallin, a member of the small heat shock family of proteins, has been implicated in a variety of cardiomyopathies and in normal cardiac homeostasis. It is known to function as a molecular chaperone, particularly for desmin, but also interacts with a wide variety of additional proteins. The molecular chaperone function is also enhanced by signal-dependent phosphorylation at specific residues under stress conditions. Naturally occurring mutations in , the gene that encodes alpha-B-crystallin, have been suggested to alter ionic intermolecular interactions that affect dimerization and chaperone function. These mutations have been associated with myofibrillar myopathy, restrictive cardiomyopathy, and hypertrophic cardiomyopathy and promote pathological hypertrophy through different mechanisms such as desmin aggregation, increased reductive stress, or activation of calcineurin-NFAT signaling. This review will discuss the known mechanisms by which alpha-B-crystallin functions in cardiac homeostasis and the pathogenesis of cardiomyopathies and provide insight into potential future areas of exploration.
αB-晶状体蛋白是小热休克蛋白家族的成员之一，与多种心肌病以及正常心脏内环境稳定有关。已知它作为分子伴侣发挥作用，尤其是对结蛋白而言，但它也与多种其他蛋白质相互作用。在应激条件下，特定残基处的信号依赖性磷酸化也会增强分子伴侣功能。编码αB-晶状体蛋白的基因发生的自然突变，被认为会改变影响二聚化和伴侣功能的离子分子间相互作用。这些突变与肌原纤维肌病、限制性心肌病和肥厚性心肌病有关，并通过不同机制促进病理性肥大，如结蛋白聚集、还原应激增加或钙调神经磷酸酶-NFAT信号通路激活。本综述将讨论αB-晶状体蛋白在心脏内环境稳定和心肌病发病机制中发挥作用的已知机制，并深入探讨未来潜在的探索领域。
