Genetic and Pathophysiological Basis of Cardiac and Skeletal Muscle Laminopathies

Genes (Basel). 2024 Aug 20;15(8):1095. doi: 10.3390/genes15081095.

Abstract

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.

Keywords: Nrf2-signaling; aging; autophagy-signaling; cardiomyopathy and skeletal muscle dysfunction; laminopathies; redox-homeostasis.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiomyopathies / genetics
  • Cardiomyopathies / metabolism
  • Cardiomyopathies / pathology
  • Cardiomyopathies / physiopathology
  • Humans
  • Laminopathies* / genetics
  • Laminopathies* / pathology
  • Lamins / genetics
  • Lamins / metabolism
  • Muscle, Skeletal* / metabolism
  • Muscle, Skeletal* / pathology
  • Muscular Dystrophies / genetics
  • Muscular Dystrophies / metabolism
  • Muscular Dystrophies / pathology
  • Mutation
  • Myocardium / metabolism
  • Myocardium / pathology
  • Signal Transduction / genetics

Substances

  • Lamins

Grants and funding

This work was supported by an AMC-21 grant for UAB, Heersink School of Medicine to GCM. This work is also supported by UAB Startup funds 3123226 and 3123227 to GCM.