PDF(Pubmed)
Abstract：
This review presents a comprehensive exploration of the pivotal role played by the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, with a particular focus on Nesprin proteins, in cellular mechanics and the pathogenesis of muscular diseases. Distinguishing itself from prior works, the analysis delves deeply into the intricate interplay of the LINC complex, emphasizing its indispensable contribution to maintaining cellular structural integrity, especially in mechanically sensitive tissues such as cardiac and striated muscles. Additionally, the significant association between mutations in Nesprin proteins and the onset of Dilated Cardiomyopathy (DCM) and Emery-Dreifuss Muscular Dystrophy (EDMD) is highlighted, underscoring their pivotal role in disease pathogenesis. Through a comprehensive examination of DCM and EDMD cases, the review elucidates the disruptions in the LINC complex, nuclear morphology alterations, and muscular developmental disorders, thus emphasizing the essential function of an intact LINC complex in preserving muscle physiological functions. Moreover, the review provides novel insights into the implications of Nesprin mutations for cellular dynamics in the pathogenesis of muscular diseases, particularly in maintaining cardiac structural and functional integrity. Furthermore, advanced therapeutic strategies, including rectifying Nesprin gene mutations, controlling Nesprin protein expression, enhancing LINC complex functionality, and augmenting cardiac muscle cell function are proposed. By shedding light on the intricate molecular mechanisms underlying nuclear-cytoskeletal interactions, the review lays the groundwork for future research and therapeutic interventions aimed at addressing genetic muscle disorders.
摘要：
这篇综述全面探索了核骨架和细胞骨架（LINC）复合物的接头所起的关键作用，特别关注奈斯普林蛋白，在细胞力学和肌肉疾病的发病机理中。区别于以前的作品，分析深入研究了LINC复合体的复杂相互作用，强调其对维持细胞结构完整性不可或缺的贡献，特别是在机械敏感的组织，如心脏和横纹肌。此外,强调了Nesprin蛋白突变与扩张型心肌病（DCM）和Emery-Dreifuss肌营养不良（EDMD）的发病之间的显着关联，强调它们在疾病发病机制中的关键作用。通过对DCM和EDMD病例的全面检查，这篇评论阐明了LINC复合体的中断，核形态学改变，和肌肉发育障碍，因此强调了完整的LINC复合物在保持肌肉生理功能方面的基本功能。此外，这篇综述为Nesprin突变对肌肉疾病发病机制中细胞动力学的影响提供了新的见解，特别是在保持心脏结构和功能的完整性。此外，先进的治疗策略，包括纠正Nesprin基因突变,控制Nesprin蛋白表达，增强LINC复杂功能，并提出了增强心肌细胞功能的方法。通过阐明核-细胞骨架相互作用的复杂分子机制，这篇综述为未来旨在解决遗传性肌肉疾病的研究和治疗干预奠定了基础.
