WNT5a-Mediated Aberrant Actin Filament Dynamics Drive Cardiac Pathogenic Phenotypes in LMNA-Related Emery-Dreifuss Muscular Dystrophy - PubMed
2 hours ago
- #WNT5a
- #LMNA-related EDMD
- #actin dynamics
- LMNA-related Emery-Dreifuss muscular dystrophy (EDMD) leads to severe cardiac issues like arrhythmias and contractile dysfunction.
- iPSC-derived cardiomyocytes from EDMD patients show disorganized sarcomeres, abnormal nuclear envelopes, and reduced WNT5A transcription due to LMNA mutation.
- WNT5a/RhoA signaling inactivation causes actin depolymerization, impairing nuclear envelope structure, contractility, and Cx43 trafficking, contributing to arrhythmias.
- Pharmacological interventions with WNT5a, RhoA activator, or actin stabilizers rescue pathogenic phenotypes in EDMD models.
- Activating WNT5a/RhoA and stabilizing actin filaments are proposed as new therapeutic strategies for LMNA-related EDMD.