eATP/P2X7R Axis: An Orchestrated Pathway Triggering Inflammasome Activation in Muscle Diseases

• Published in: International journal of molecular sciences Vol. 21; no. 17; p. 5963
• Main Authors: Panicucci, Chiara, Raffaghello, Lizzia, Bruzzone, Santina, Baratto, Serena, Principi, Elisa, Minetti, Carlo, Gazzerro, Elisabetta, Bruno, Claudio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19-08-2020; MDPI
• Subjects: Adenosine triphosphate; Adenosine Triphosphate - metabolism; Animal models; Animals; Apoptosis; Crosstalk; Damage patterns; Duchenne Muscular Dystrophy; eATP; Environmental effects; Feedback control; Foxp3 protein; Humans; Immune system; inflammasome; Inflammasomes; Inflammasomes - metabolism; Inflammation; Inflammatory response; Kinases; Lymphocytes; Lymphocytes T; Membranes; Muscle, Skeletal - metabolism; Muscles; muscular dystrophies; Muscular Dystrophies - metabolism; Musculoskeletal system; P2X7R; Phenotypes; Phosphorylation; Physiology; Proteins; Receptors, Purinergic P2X7 - metabolism; Review; Sarcoglycanopathies; Signal Transduction; Transcription; Duchenne Muscular Dystrophy; muscular dystrophies; eATP; inflammasome; P2X7R; Sarcoglycanopathies
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21175963

In muscle ATP is primarily known for its function as an energy source and as a mediator of the "excitation-transcription" process, which guarantees muscle plasticity in response to environmental stimuli. When quickly released in massive concentrations in the extracellular space as in presence of muscle membrane damage, ATP acts as a damage-associated molecular pattern molecule (DAMP). In experimental murine models of muscular dystrophies characterized by membrane instability, blockade of eATP/P2X7 receptor (R) purinergic signaling delayed the progression of the dystrophic phenotype dampening the local inflammatory response and inducing Foxp3
T Regulatory lymphocytes. These discoveries highlighted the relevance of ATP as a harbinger of immune-tissue damage in muscular genetic diseases. Given the interactions between the immune system and muscle regeneration, the comprehension of ATP/purinerigic pathway articulated organization in muscle cells has become of extreme interest. This review explores ATP release, metabolism, feedback control and cross-talk with members of muscle inflammasome in the context of muscular dystrophies.