Unraveling the nexus of nesprin in dilated cardiomyopathy: From molecular insights to therapeutic prospects.

Life Sci

Department of Cardiology, Yichang Central People's Hospital/The First Clinical Medical College, Three Gorges University, Yichang 443003, Hubei, People's Republic of China; King's College London British Heart Foundation Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, London SE5 9NU, UK. Electronic address:

Published: December 2024

AI Article Synopsis

  • Dilated cardiomyopathy is a serious heart condition where the heart chambers enlarge and weaken, causing difficulty in pumping blood and heart failure.
  • Nesprins, which are proteins that connect the nuclear envelope and cytoskeleton, are important for maintaining heart muscle structure and function, especially in the context of dilated cardiomyopathy.
  • Mutations in genes related to Nesprin-1 and Nesprin-2 have been linked to this heart disorder, suggesting their critical role in cardiac health and potential targets for new treatments.

Article Abstract

Dilated cardiomyopathy is a complex and debilitating heart disorder characterized by the enlargement and weakening of the cardiac chambers, leading to impaired contractility and heart failure. Nesprins, a family of nuclear envelope spectrin repeat proteins that include isoforms Nesprin-1/-2, are integral components of the LInker of Nucleoskeleton and Cytoskeleton complex. They facilitate the connection between the nuclear envelope and the cytoskeleton, crucial for maintaining nuclear architecture, migration and positioning, and mechanical transduction and signaling. Nesprin-1/-2 are abundantly expressed in cardiac and skeletal muscles.They have emerged as key players in the pathogenesis of dilated cardiomyopathy. Mutations in synaptic nuclear envelope-1/-2 genes encoding Nesprin-1/-2 are associated with dilated cardiomyopathy, underscoring their significance in cardiac health. This review highlights the all known cases of Nesprin-1/-2 related dilated cardiomyopathy, focusing on their interactions with the nuclear envelope, their role in mechanical transduction, and their influence on gene expression. Moreover, it delves into the underlying mechanisms through which Nesprin dysfunction disrupts nuclear-cytoskeletal coupling, leading to abnormal nuclear morphology, impaired mechanotransduction, and altered gene regulation. The exploration of Nesprin's impact on dilated cardiomyopathy offers a promising avenue for therapeutic interventions aimed at ameliorating the disease. This review provides a comprehensive overview of recent advancements in understanding the pivotal role of Nesprins in dilated cardiomyopathy research.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2024.123126DOI Listing

Publication Analysis

Top Keywords

dilated cardiomyopathy
28
nuclear envelope
12
mechanical transduction
8
dilated
7
cardiomyopathy
7
nuclear
6
unraveling nexus
4
nexus nesprin
4
nesprin dilated
4
cardiomyopathy molecular
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!