Department of Biology, Molecular Biology Institute, San Diego State University, San Diego, CA 92182, USA.
Department of Pathology, Division of Molecular and Cellular Pathology, Heersink School of Medicine, University of Alabama, Birmingham, AL 35294, USA.
Genes (Basel). 2024 Aug 20;15(8):1095. doi: 10.3390/genes15081095.
Nuclear lamins, a type V intermediate filament, are crucial components of the nuclear envelope's inner layer, maintaining nuclear integrity and mediating interactions between the nucleus and cytoplasm. Research on human iPSC-derived cells and animal models has demonstrated the importance of lamins in cardiac and skeletal muscle development and function. Mutations in lamins result in laminopathies, a group of diseases including muscular dystrophies, Hutchison-Gilford progeria syndrome, and cardiomyopathies with conduction defects. These conditions have been linked to disrupted autophagy, mTOR, Nrf2-Keap, and proteostasis signaling pathways, indicating complex interactions between the nucleus and cytoplasm. Despite progress in understanding these pathways, many questions remain about the mechanisms driving lamin-induced pathologies, leading to limited therapeutic options. This review examines the current literature on dysregulated pathways in cardiac and skeletal muscle laminopathies and explores potential therapeutic strategies for these conditions.
核纤层蛋白是一种 V 型中间丝，是核膜内层的重要组成部分，维持核的完整性，并介导核与细胞质之间的相互作用。对人类 iPSC 衍生细胞和动物模型的研究表明，核纤层蛋白在心脏和骨骼肌发育和功能中起着重要作用。核纤层蛋白的突变导致核纤层病，这是一组疾病，包括肌肉营养不良症、Hutchison-Gilford 早老综合征和伴有传导缺陷的心肌病。这些情况与自噬、mTOR、Nrf2-Keap 和蛋白稳态信号通路的破坏有关，表明核与细胞质之间存在复杂的相互作用。尽管在理解这些通路方面取得了进展，但对于驱动核纤层蛋白引起的病理学的机制仍存在许多问题，导致治疗选择有限。这篇综述检查了心脏和骨骼肌核纤层病中失调通路的现有文献，并探讨了这些疾病的潜在治疗策略。
