P2 Receptor Signaling in Motor Units in Muscular Dystrophy

Abstract

The purine signaling system is represented by purine and pyrimidine nucleotides and nucleosides that exert their effects through the adenosine, P2X and P2Y receptor families. It is known that, under physiological conditions, P2 receptors play only a minor role in modulating the functions of cells and systems; however, their role significantly increases under some pathophysiological conditions, such as stress, ischemia or hypothermia, when they can play a dominant role as a signaling molecule. The diversity of P2 receptors and their wide distribution in the body make them very attractive as a target for the pharmacological action of drugs with a new mechanism of action. The review is devoted to the involvement of P2 signaling in the development of pathologies associated with a loss of muscle mass. The contribution of adenosine triphosphate (ATP) as a signal molecule in the pathogenesis of a number of muscular dystrophies (Duchenne, Becker and limb girdle muscular dystrophy 2B) is considered. To understand the processes involving the purinergic system, the role of the ATP and P2 receptors in several models associated with skeletal muscle degradation is also discussed.

The Role of P2X7 Purinoceptors in the Pathogenesis and Treatment of Muscular Dystrophies

“…Importantly, in addition to the lost ecto-ATPase activity of α-sarcoglycan, a purinergic receptor abnormality was identified in a range of dystrophic cells. Several studies using a combination of molecular, biochemical, functional, and immunodetection methods identified alterations in the expression and function of specific purinoceptors in dystrophic muscle [64][65][66]. In contrast to their aforementioned physiological expression, ionotropic P2X2, P2X5, and P2X6 [45] as well as metabotropic P2Y2 and P2Y4 receptors [65], were found altered in dystrophy.…”

Next Generation Sequencing and Electromyography Reveal the Involvement of the P2RX6 Gene in Myopathy

“…Several muscular and neurological disorders characterized by motor symptoms have been associated with variations in the expression and function of purinergic receptors. Therefore, numerous studies have proposed a potentially robust association between disruption in purinergic receptors and the development of myopathy [25,26]. In fact, neuromodulators like purinergic ligands, adenosine, and ATP serve as signaling molecules with specific roles in different muscular pain syndromes.…”