TWEAK/Fn14, a pathway and novel therapeutic target in myotonic dystrophy.

ABSTRACT: Myotonic dystrophy type 1 (DM1), the most prevalent muscular dystrophy in adults, is characterized by progressive muscle wasting and multi-systemic complications. DM1 is the prototype for disorders caused by RNA toxicity. Currently, no therapies exist. Here, we identify that fibroblast growth factor-inducible 14 (Fn14), a member of the tumor necrosis factor receptor super-family, is induced in skeletal muscles and hearts of mouse models of RNA toxicity and in tissues from DM1 patients, and that its expression correlates with severity of muscle pathology. This is associated with downstream signaling through the NF-κB pathways. In mice with RNA toxicity, genetic deletion of Fn14 results in reduced muscle pathology and better function. Importantly, blocking TWEAK/Fn14 signaling with an anti-T

SUBMITTER: Yadava RS 

PROVIDER: S-EPMC4355029 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature