Figure 5.

Scheme of mechanisms that might contribute to the dystrophy progression in dysferlinopathies. (a) In a healthy condition, the damage in plasma membrane is rapidly repaired, and only a local increase of Ca²⁺ is produced. (b) In a dysferlinopathy condition, the membrane repair is impaired [6], and non-selective channels, such as connexin-based hemichannels, P2X₇ receptors and transient receptor potential TRPV2 channels are de novo expressed [56,57]. This could contribute to an altered Ca²⁺ homeostasis [56], mitochondrial dysfunction [12], ROS production [13], and consequently OS, resulting in lipid peroxidation (LpOx) and protein oxidation (P Ox) [4]. OS further conduces to the activation of the NF-κB inflammatory signaling pathway [58]. On the other hand, an altered Ca²⁺ homeostasis might also lead to the activation of breakdown protein pathways such as calpains, ubiquitin-proteasome pathway and autophagy [59], whose overactivation also results muscle atrophy [60]. NAC reduces OS and NF-κB inflammatory signaling pathway [61].