Modulation of the neuronal network activity by P2X receptors and their involvement in neurological disorders

ATP is a key energetic molecule, fundamental to cell function, which also has an important role in the extracellular milieu as a signaling molecule, acting as a chemoattractant for immune cells and as a neuro- and gliotransmitter. The ionotropic P2X receptors are members of an ATP-gated ion channels family. These ionotropic receptors are widely expressed through the body, with 7 subunits described in mammals, which are arranged in a trimeric configuration with a central pore permeable mainly to Ca²⁺ and Na⁺. All 7 subunits are expressed in different brain areas, being present in neurons and glia. ATP, through these ionotropic receptors, can act as a neuromodulator, facilitating the Ca²⁺-dependent release of neurotransmitters, inducing the cross-inhibition between P2XR and GABA receptors, and exercising by this way a modulation of synaptic plasticity. Growing evidence shows that P2XR play an important role in neuronal disorders and neurodegenerative diseases, like Parkinson's and Alzheimer's disease; this role involves changes on P2XR expression levels, activation of key pathways like GSK3β, APP processing, oxidative stress and inflammatory response. This review is focused on the neuromodulatory function of P2XR on pathophysiological conditions of the brain; the recent evidence could open a window to a new therapeutic target.