P2X RECEPTORS AS A NOVEL PROMINENT PHARMACOLOGICAL TARGET FOR VARIOUS CNS DISORDERS [

Abstract

Purinergic P2X receptors, particularly P2X7 and P2X4, are pivotal in brain functioning and pathology, affecting various central nervous system diseases. This review delves into P2X receptors’ roles in various pathologies, including ischemia, epilepsy, COVID-19, some neurodegenerative and psychiatric disorders. P2X7’s involvement in neuroinflammatory processes through the activation of the NLRP3 inflammasome highlights its significant role in corresponding pathologies and their treatment, as seen in studies using selective receptor antagonists like JNJ-55308942. Similarly, P2X4 receptor, which has the higher sensitivity to ATP than P2X7, plays critical roles in the inflammatory response poststroke and show therapeutic potential across a spectrum of neurological conditions. The emerging significance of P2X receptors in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and Amyotrophic Lateral Sclerosis, showcasing their influence on disease progression and potential as therapeutic targets is also briefly discussed. In psychiatric disorders, including major depressive disorder and autism spectrum disorders, P2X receptors contribute to pathology through mechanisms involving inflammation and neuroimmune response modulation. In summary, the recent data underscores the importance of P2X receptors in CNS health and disease, advocating for further exploration to uncover novel therapeutic strategies.