Glial purinergic receptors: roles in CNS function, and therapeutic potential in neurological disorders
| Receptor type | Role in CNS | Therapeutic potential | References |
|---|---|---|---|
| P2X1 | Regulates cerebral blood flow, neurovascular coupling, and blood-brain barrier function | Modulation could improve ischemic stroke outcomes by enhancing blood flow and neurovascular responses | [362–364] |
| P2X4 | Involved in neuropathic pain signaling, synaptic plasticity, microglial activation, and cytokine release | Antagonists are being studied for neuropathic pain and chronic inflammatory conditions | [180, 181, 365] |
| P2X5 | Modulates glial cell proliferation and inflammatory responses | Targeting P2X5 receptors could regulate gliosis, neuroinflammation, and neurodegeneration | [366–368] |
| P2X7 | Drives inflammasome activation, cytokine release, and neuroinflammation. Involved in Alzheimer’s, Parkinson’s, and multiple sclerosis pathophysiology | Antagonists (e.g., BBG) reduce neuroinflammation and neurodegeneration in various CNS diseases | [66, 240, 313, 326, 369, 370] |
| P2Y1 | Modulates microglial activation, neuronal excitability, and blood-brain barrier integrity | Targeting P2Y1 receptors could aid in conditions like multiple sclerosis and traumatic brain injury | [104, 119, 371] |
| P2Y6 | Facilitates phagocytosis, aiding in the clearance of cellular debris and neurotoxic aggregates | Enhancing P2Y6 activity could help clear amyloid plaques in Alzheimer’s and alpha-synuclein in Parkinson’s | [272, 372–374] |
| P2Y12 | Essential for microglial chemotaxis and inflammatory response | Targeting P2Y12 receptors may improve recovery and reduce damage in stroke, Alzheimer’s, and other CNS injuries | [115, 375–377] |
| P2Y13 | Modulates microglial migration, activation, synaptic plasticity, and neuroinflammation | Antagonists may regulate glial activation in neurodegenerative diseases and acute CNS injuries | [264, 267, 378] |
| A1 adenosine | Reduces excitotoxicity, regulates neurotransmitter release, and provides neuroprotection, particularly during ischemic events | A1 receptor agonists are potential treatments for ischemia, epilepsy, and neurodegenerative diseases | [379–382] |
| A2A adenosine | Modulates neuroinflammation, synaptic plasticity, and myelination. Suppresses pro-inflammatory cytokine release | A2A antagonists could reduce neuroinflammation and improve dopaminergic signaling in Parkinson’s disease | [194, 302, 382, 383] |
BBG: Brilliant Blue G; CNS: central nervous system