Targeting P2X4 and P2X7 receptors in multiple sclerosis. (August 2019)

• Record Type: Journal Article
• Authors: Domercq, María; Matute, C
• Is Part Of: Current opinion in pharmacology. Volume 47(2019)
• Page Start: 119
• Page End: 125
• Publication Date: 2019-08
• Subjects: Pharmacology -- Periodicals; Pharmaceutical Preparations -- Periodicals; Drug Therapy -- Periodicals; Biopharmaceutics -- Periodicals; Pharmacologie -- Périodiques; Pharmacology; Periodicals; 615.105
• DOI: 10.1016/j.coph.2019.03.010
• Languages: English
• ISSNs: 1471-4892

Abstract

Highlights: EAE clinical signs are exacerbated by P2X4 receptor blockage and ameliorated by its potentiation with the allosteric modulator ivermectin. P2X4 receptor activation increases myelin phagocytosis and promotes BDNF release, thus favoring remyelination. P2X7 receptor overactivation contributes to primary oligodendrocyte death and controls inflammasome activation in myeloid cells. P2X7 receptor antagonists delay the onset of EAE and attenuates its symptoms. Abstract : Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by massive infiltration of immune cells, demyelination, and axonal loss. However, spontaneous myelin repair can occur during the course of the disease. A major component of this regenerative process is a robust innate immune response consisting of infiltrating macrophages and brain microgliosis. Therefore, specifically targeting myeloid cells could be an attractive therapeutic approach. Purinergic receptors control not only immune cell function together with the activation of microglia and astrocytes, but also neuronal and oligodendroglial survival in the pathology. Thus, targeting these receptors can modulate a whole variety of responses. In this review, we will summarize recent findings highlighting the potential of P2X4 and P2X7 as therapeutic targets for MS.