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Review

P2X7 Receptors Amplify CNS Damage in Neurodegenerative Diseases

by 1,2
1
Rudolf Boehm Institute for Pharmacology and Toxicology, University of Leipzig, 04107 Leipzig, Germany
2
International Collaborative Centre on Big Science Plan for Purinergic Signalling, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
Int. J. Mol. Sci. 2020, 21(17), 5996; https://doi.org/10.3390/ijms21175996
Received: 26 June 2020 / Revised: 7 August 2020 / Accepted: 17 August 2020 / Published: 20 August 2020
(This article belongs to the Collection Feature Papers in Molecular Pharmacology)
ATP is a (co)transmitter and signaling molecule in the CNS. It acts at a multitude of ligand-gated cationic channels termed P2X to induce rapid depolarization of the cell membrane. Within this receptor-channel family, the P2X7 receptor (R) allows the transmembrane fluxes of Na+, Ca2+, and K+, but also allows the slow permeation of larger organic molecules. This is supposed to cause necrosis by excessive Ca2+ influx, as well as depletion of intracellular ions and metabolites. Cell death may also occur by apoptosis due to the activation of the caspase enzymatic cascade. Because P2X7Rs are localized in the CNS preferentially on microglia, but also at a lower density on neuroglia (astrocytes, oligodendrocytes) the stimulation of this receptor leads to the release of neurodegeneration-inducing bioactive molecules such as pro-inflammatory cytokines, chemokines, proteases, reactive oxygen and nitrogen molecules, and the excitotoxic glutamate/ATP. Various neurodegenerative reactions of the brain/spinal cord following acute harmful events (mechanical CNS damage, ischemia, status epilepticus) or chronic neurodegenerative diseases (neuropathic pain, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis) lead to a massive release of ATP via the leaky plasma membrane of neural tissue. This causes cellular damage superimposed on the original consequences of neurodegeneration. Hence, blood-brain-barrier permeable pharmacological antagonists of P2X7Rs with excellent bioavailability are possible therapeutic agents for these diseases. The aim of this review article is to summarize our present state of knowledge on the involvement of P2X7R-mediated events in neurodegenerative illnesses endangering especially the life quality and duration of the aged human population. View Full-Text
Keywords: P2X7 receptor; neuroinflammation; neurodegenerative diseases; mechanical injury; ischemia; epilepsy; neuropathic pain; Alzheimer’s disease; Parkinson’s disease; multiple sclerosis; amyotrophic lateral sclerosis P2X7 receptor; neuroinflammation; neurodegenerative diseases; mechanical injury; ischemia; epilepsy; neuropathic pain; Alzheimer’s disease; Parkinson’s disease; multiple sclerosis; amyotrophic lateral sclerosis
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MDPI and ACS Style

Illes, P. P2X7 Receptors Amplify CNS Damage in Neurodegenerative Diseases. Int. J. Mol. Sci. 2020, 21, 5996. https://doi.org/10.3390/ijms21175996

AMA Style

Illes P. P2X7 Receptors Amplify CNS Damage in Neurodegenerative Diseases. International Journal of Molecular Sciences. 2020; 21(17):5996. https://doi.org/10.3390/ijms21175996

Chicago/Turabian Style

Illes, Peter. 2020. "P2X7 Receptors Amplify CNS Damage in Neurodegenerative Diseases" International Journal of Molecular Sciences 21, no. 17: 5996. https://doi.org/10.3390/ijms21175996

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