A Novel Class of FKBP12 Ligands Rescues Premature Aging Phenotypes Associated with Myotonic Dystrophy Type 1.

ABSTRACT: Background: Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder clinically characterized by progressive muscular weakness and multisystem degeneration, which correlates with the size of CTG expansion and MBLN decrease. These changes induce a calcium and redox homeostasis imbalance in several models that recapitulate the features of premature tissue aging. In this study, we characterized the impact of a new family of FKBP12 ligands (generically named MPs or MP compounds) designed to stabilize FKBP12 binding to the ryanodine receptors and normalize calcium dysregulation under oxidative stress. Methods: Human primary fibroblasts from DM1 patients and control donors, treated with MP compounds or not, were used for functional studies of cell viability, proliferation,

SUBMITTER: Garcia-Puga M 

PROVIDER: S-EPMC11639790 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature