Journal ArticleDOI
Physiopathological roles of P2X receptors in the central nervous system.
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TLDR
Seven P2X ion channel receptor subtypes participate in CNS pathophysiology, including injury, inflammation, Alzheimer's and Parkinson's diseases, multiple sclerosis and amyotrophic lateral sclerosis, depression and anxiety.Abstract:
Potent actions of ATP in the central nervous system (CNS) were reported in the late 1940's, but cloning and characterisation of receptors for purines and pyrimidines did not take place until the early 1990's, which identified seven P2X ion channel receptor subtypes, three of which form the cation channel as homomultimers or heteromultimers. P2X receptor subtypes are widely expressed in the CNS and their distribution is described in different regions. They function in synaptic cotransmission and neuromodulation, as well as in trophic signalling. ATP released from nerves and astroglial cells are predominantly involved in neuron-glial interactions. Purinergic signalling is involved in normal behaviour, including learning and memory, sleep and arousal, locomotor and feeding activities and cognition. P2X receptors participate in CNS pathophysiology, including injury, inflammation, Alzheimer's and Parkinson's diseases, multiple sclerosis and amyotrophic lateral sclerosis, depression and anxiety. P2X4 and P2X7 receptor antagonists are effective via microglia against neuropathic pain, while P2X3 receptor antagonists also reduce neuropathic pain, but via a different mechanism.read more
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Journal ArticleDOI
Purinergic Signalling: Therapeutic Developments.
TL;DR: Investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.
Journal ArticleDOI
Medicinal chemistry of adenosine, P2Y and P2X receptors.
TL;DR: There are definitive, selective agonists and antagonists for all of the ARs and some of the P2YRs; while the pharmacochemistry of P2XRs is still in nascent stages.
Journal ArticleDOI
The potential of P2X7 receptors as a therapeutic target, including inflammation and tumour progression.
TL;DR: Seven P2X ion channel nucleotide receptor subtypes have been cloned and characterised and the potential of P2x7R antagonists to treat a variety of diseases including neurodegenerative diseases, psychiatric disorders, epilepsy and a number of diseases of peripheral organs.
Journal ArticleDOI
An introduction to the roles of purinergic signalling in neurodegeneration, neuroprotection and neuroregeneration
TL;DR: The roles of purinergic signalling in trauma, ischaemia, stroke and in neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's diseases, as well as multiple sclerosis and amyotrophic lateral sclerosis are considered.
Journal ArticleDOI
Pharmacology of a Novel Central Nervous System–Penetrant P2X7 Antagonist JNJ-42253432
Brian Lord,Leah Aluisio,James R. Shoblock,Robert Neff,Elena I. Varlinskaya,Marc Ceusters,Timothy W. Lovenberg,Nicholas I. Carruthers,Pascal Bonaventure,Michael A. Letavic,Terrence Deak,Wilhelmus Drinkenburg,Anindya Bhattacharya +12 more
TL;DR: JNJ-42253432 is characterized as a novel brain-penetrant P 2X7 antagonist with high affinity and selectivity for the P2X7 channel and significantly increased both overall social interaction and social preference, an effect that was independent of stress induced by foot-shock.