Purinergic signalling at the plasma membrane: a multipurpose and multidirectional mode to deal with amyotrophic lateral sclerosis and multiple sclerosis

ATP is a widespread and multipurpose signalling molecule copiously released in the extracellular environment of the whole nervous system upon cell activation, stress, or damage. Extracellular ATP is also a multidirectional information molecule, given the concurrent presence at the plasma membrane of various targets for ATP. These include ectonucleotidases (metabolizing ATP down to adenosine), ATP/adenosine transporters, P2 receptors for purine/pyrimidine nucleotides (ligand-gated ion channels P2X receptors and G-protein-coupled P2Y receptors), in addition to metabotropic P1 receptors for nucleosides. All these targets rarely operate as single units, rather they associate with each other at the plasma membrane as multi-protein complexes. Altogether, they control the duration, magnitude and/or direction of the signals triggered and propagated by purine/pyrimidine ligands, and the impact that each single ligand has on a variety of short- and long-term functions. A strict control system allows assorted, even divergent, biological outcomes. Among these, we enumerate cell-to-cell communication, tropic, trophic, but also noxious actions causing the insurgence/progression of pathological conditions. Here, we show that purinergic signalling in the nervous system can be instrumental for instance to neurodegenerative and neuroinflammatory diseases such as amyotrophic lateral sclerosis and multiple sclerosis.