Membrane compartments and purinergic signalling: P2X receptors in neurodegenerative and neuroinflammatory events

ATP is a potent signalling molecule abundantly present in the nervous system, where it exerts physiological actions ranging from short-term responses such as neurotransmission, neuromodulation and glial communication, to long-term effects such as trophic actions. The fast signalling targets of extracellular ATP are represented by the ionotropic P2X receptors, which are broadly and abundantly expressed in neurons and glia in the whole central and peripheral nervous systems. Because massive extracellular release of ATP often occurs by lytic and non-lytic mechanisms, especially after stressful events and pathological conditions, purinergic signalling is correlated to and involved in the aetiopathology and/or progression of many neurodegenerative diseases. In this minireview, we highlight the contribution of the subclass of ionotropic P2X receptors to several diseases of the human nervous system, such as neurodegenerative disorders and immune-mediated neuroinflammatory dysfunctions including ischaemia, Parkinson's, Alzheimer's and Huntington's diseases, amyotrophic lateral sclerosis and multiple sclerosis. The role of P2X receptors as novel and effective targets for the genetic/pharmacological manipulation of purinergic mechanisms in several neuropathological conditions is now well established. Nevertheless, any successful therapeutic intervention against these diseases cannot be restricted to P2X receptors, but should take into consideration the whole and multipart ATP signalling machinery.