Table Info

Table 4.

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

Declarations

Author contributions

MMN: Conceptualization, Writing—original draft, Writing—review & editing.

Conflicts of interest

The author declares that there are no conflicts of interest.

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