α7-Nicotinic acetylcholine receptors: an old actor for new different roles.
In the years from 1856 to 1936, when the Nobel Prize for Physiology/Medicine was awarded to Dale and Loewi " for their discoveries relating to chemical transmission of nerve impulses" , the nicotinic acetylcholine receptor (nAChR) emerged from an assumption to a reality. Its biochemical isolation in 1970 represents a major breakthrough in pharmacology. The α7-nAChR subunit forms homo-oligodimeric nAChR with unique distinctive properties, such as high permeability to calcium and modulation by the extracellular calcium concentrations, the possibility of binding two-five molecules of agonist, function modulation via phosphorylation and/or via calcium-dependent serine/threonine kinases and modulating transmitter release and activation of GABAergic interneurons. In the brain, the α7-nAChR plays several important functions running from synaptic plasticity, regulation of neuronal growth, differentiation and survival to enhance learning and cognition. The detection of its occurrence on non-neuronal cells raises question related to their specific activity, since in these cells it appears involved in modulation of cell death, migration and signaling. Its unbalance might involve it in different diseases such as Alzheimer, Parkinson and cancer. However, the peculiarity of α7-nAChR offers rational bases to develop new drugs and new therapeutic strategies. In conclusion, α7-nAChR roughly in 150 years of life, instead to be an old actor became an important player in regulating cell signaling.
Laboratory of Systems Approaches and Non Communicable Diseases, IRCCS San Raffaele Pisana, Rome, Italy. patrizia_russo@hotmail.it
Patrizia
P
Russo
Antoine
A
Taly
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D009474:Neurons / Q000378:metabolism; D010539:Permeability; D011978:Receptors, Nicotinic / Q000378:metabolism*; D015398:Signal Transduction; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D002118:Calcium