P2X7 purinoceptor involvement in the dystrophic pathology.
Absence of dystrophin and resulting loss of the DAP complex lead to myofiber damage. Degenerating/dying muscle releases large quantities of DAMPs, including ATP, which trigger chronic inflammation. P2RX7 activation on dystrophic myofibers exacerbates injury by promoting intracellular Ca2+ build-up and autophagic cell death. Infiltrating macrophages (Mφ), T-cells, and granulocytes (GrC) cause further myofiber damage, while chronically elevated levels of inflammatory mediators disturb normal brain and bone functions. Chronic inflammation also reduces repair by altering satellite cell (SC) activation and muscle precursor cell differentiation, while high eATP levels combined with P2RX7 overexpression contribute to their death and thus reduce muscle regeneration further still.