A recent study analyzed the role of purinergic receptor P2X4 in microglia/macrophages during autoimmune inflammation, finding that P2X4 receptors modulate microglia/macrophage inflammatory responses and identify allosteric modulator ivermectin (IVM) as a potential candidate to promote the repair of myelin damage.
Multiple sclerosis (MS) is a chronic inflammatory disease of the brain and spinal cord that attacks and destroys the myelin sheath, leading to demyelination and neurodegeneration. A recent study analyzed the role of purinergic receptor P2X4 (P2X4R) in microglia/macrophages during autoimmune inflammation, finding that P2X4Rs modulate microglia/macrophage inflammatory responses and identify allosteric modulator ivermectin (IVM) as a potential candidate to promote the repair of myelin damage.
The study, published by EMBO Molecular Medicine, explained how microglia survey the brain microenvironment for signals of injury or infection; understanding these mechanisms of microglia responses during pathology are important for promoting regenerative responses. The researchers were able to identify the receptor P2X4 present in the microglial cells that increases the antiinflammatory potential and encourages the body’s own repair responses.
“Innate immune cells contribute to axonal damage and demyelination in MS but they are also pivotal in promoting repair responses. Modulating microglia/macrophage P2X4R activation determines clinical outcome in the experimental autoimmune encephalomyelitis (EAE) model of MS,” the study stated.
The experiment was conducted using animal models of the disease, which revealed that the drugs that activate the P2X4R receptor also improve the symptoms during the chronic phase of the disease when continuing the repair of nervous tissue.
The main findings of the study, involving P2X4R included:
Specifically, the researchers emphasized that the P2X4R signaling by the IVM favored a switch in microglia to an antiinflammatory phenotype, potentiated myelin phagocytosis, promoted the remyelination response, and ameliorated clinical signs of EAE.
“Mechanistically, P2X4 receptor signaling potentiation in microglia/macrophages favors a switch to an anti‐inflammatory phenotype that, by secreting factors such as BDNF and increasing myelin phagocytosis, leads to higher remyelination,” explained the researchers. “Altogether, data here suggest that P2X4R upregulation could be a marker of the neuroinflammatory response in MS and that potentiation of signaling by P2X4R has therapeutic potential to treat demyelinating disorders.”