In the dystrophin-deficient muscle of mouse, rat and dog models of Duchenne muscular dystrophy, there is activation of necroptosis, RIPK1 and RIPK3, key signaling molecules of programmed necrosis, as well as MLKL, a downstream effector of RIPK1 and 3. However, two studies have shown that inhibition of necroptosis can lead to impaired myogenesis and muscle atrophy.
To find out more, researchers in the Paris region investigated the long-term effects of necroptosis inhibition on diaphragm and heart remodeling in RIPK3-deficient mdx mice (mdx/Ripk3-/- mice):
- these mice have a significant reduction in muscle fibrosis compared with mdxRipk3+/+ mice;
- RIPK3 deficiency reduces myocardial hypertrophy and cardiac fibrosis without generating sarcopenia.
