Targeting Mitogen-Activated Protein Kinase Signaling in Mouse Models of Cardiomyopathy Caused by Lamin A/C Gene Mutations

Methods in Enzymology
Antoine Muchir, Howard J Worman

Abstract

The most frequently occurring mutations in the gene encoding nuclear lamin A and nuclear lamin C cause striated muscle diseases virtually always involving the heart. In this review, we describe the approaches and methods used to discover that cardiomyopathy-causing lamin A/C gene mutations increase MAP kinase signaling in the heart and that this plays a role in disease pathogenesis. We review different mouse models of cardiomyopathy caused by lamin A/C gene mutations and how transcriptomic analysis of one model identified increased cardiac activity of the ERK1/2, JNK, and p38α MAP kinases. We describe methods used to measure the activity of these MAP kinases in mouse hearts and then discuss preclinical treatment protocols using pharmacological inhibitors to demonstrate their role in pathogenesis. Several of these kinase inhibitors are in clinical development and could potentially be used to treat human subjects with cardiomyopathy caused by lamin A/C gene mutations.

Citations

Sep 14, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Graham F BradyM Bishr Omary
Apr 1, 2017·American Journal of Physiology. Gastrointestinal and Liver Physiology·M Bishr Omary
Jul 9, 2016·Current Opinion in Neurology·Peter Meinke, Eric C Schirmer
Mar 20, 2018·Gastroenterology·Graham F BradyM Bishr Omary
May 1, 2021·International Journal of Molecular Sciences·Lorenzo MaggiGiovanna Lattanzi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.