Cell signaling abnormalities in cardiomyopathy caused by lamin A/C gene mutations.

Mutations in the lamin A/C gene ( LMNA ) encoding intermediate filament proteins associated with the inner nuclear membrane cause diseases known as laminopathies. Most LMNA mutations cause dilated cardiomyopathy with variable skeletal muscular dystrophy. Cell signaling abnormalities have been discovered in hearts of mouse models of cardiomyopathy caused by LMNA mutations that contribute to pathogenesis. These include abnormally increased signaling by extracellular signal-regulated kinase 1 and kinase 2 and other mitogen-activated protein kinases, protein kinase B/mammalian target of rapamycin complex 1 and transforming growth factor-β. Preclinical research suggests that specific inhibitors of these abnormally activated cell signaling pathways may be useful in treating human patients with this disease.