Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/109156
Title: ATP as a multi-target danger signal in the brain
Authors: Rodrigues, Ricardo J. 
Tomé, Ângelo R. 
Cunha, Rodrigo A. 
Keywords: ATP; adenosine; P2 receptors; P1 receptors; ecto-nucleotidases; P2X7 receptor; P2Y1 receptor; A2A receptor
Issue Date: 2015
Publisher: Frontiers Media S.A.
Serial title, monograph or event: Frontiers in Neuroscience
Volume: 9
Issue: APR
Abstract: ATP is released in an activity-dependent manner from different cell types in the brain, fulfilling different roles as a neurotransmitter, neuromodulator, in astrocyte-to-neuron communication, propagating astrocytic responses and formatting microglia responses. This involves the activation of different ATP P2 receptors (P2R) as well as adenosine receptors upon extracellular ATP catabolism by ecto-nucleotidases. Notably, brain noxious stimuli trigger a sustained increase of extracellular ATP, which plays a key role as danger signal in the brain. This involves a combined action of extracellular ATP in different cell types, namely increasing the susceptibility of neurons to damage, promoting astrogliosis and recruiting and formatting microglia to mount neuroinflammatory responses. Such actions involve the activation of different receptors, as heralded by neuroprotective effects resulting from blockade mainly of P2X7R, P2Y1R and adenosine A2A receptors (A2AR), which hierarchy, cooperation and/or redundancy is still not resolved. These pleiotropic functions of ATP as a danger signal in brain damage prompt a therapeutic interest to multi-target different purinergic receptors to provide maximal opportunities for neuroprotection.
URI: https://hdl.handle.net/10316/109156
ISSN: 1662-4548
DOI: 10.3389/fnins.2015.00148
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais
IIIUC - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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