Extracellular ATP and P2X7 receptors in neurodegeneration.
Neuronal injury and cell death in the central nervous system (CNS) are underlying features of neurodegenerative disorders. However, our understanding of the fundamental mechanisms involved is still limited. Inflammatory processes mediated by cytokines, and interleukin-1 (IL-1) in particular, play a significant role in neuronal death following pathological insults. Despite this growing area of research, very little is known about the factors regulating the expression, cleavage and release of interleukin-1 in the brain. Recent studies on immune cells demonstrate that extracellular ATP can act as a potent stimulus for the maturation and release of interleukin-1beta, via activation of P2X7 receptors. Stimulation of P2X7 receptors with ATP has dramatic cytotoxic properties and a wider role in neurodegenerative processes is possible. This review discusses the potential involvement of extracellular ATP and P2X7 receptors as regulators of interleukin-1-mediated neuropathologies and thus as a mediator of cell death following pathological insults.
Le Feuvre
Rosalind
R
School of Biological Sciences, University of Manchester, Stopford Building 1.204, Oxford Road, Manchester, M13 9PT, UK. mqbssral@man.ac.uk
Brough
David
D
Rothwell
Nancy
N
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D016207:Cytokines / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D009410:Nerve Degeneration; D019636:Neurodegenerative Diseases / Q000209:etiology*; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058486:Receptors, Purinergic P2X7
D016207:Cytokines; D007375:Interleukin-1; C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate