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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89514 |
| Date | 05 February 2024 |
| Creators | Illes, Peter |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 5996 |
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