Connexins in the Central Nervous System: Physiological Traits and Neuroprotective Targets

Abstract

Cell-to-cell interaction and cell-to-extracellular environment communication are emerging as new therapeutic targets in neurodegenerative disorders. Dynamic expression of connexins leads to distinctive hemichannels and gap junctions, characterized by cell-specific conduction, exchange of stimuli or metabolites, and particular channel functions. Herein, we briefly reviewed classical physiological traits and functions of connexins, hemichannels, and gap junctions, in order to discuss the controversial role of these proteins and their mediated interactions during neuroprotection, with a particular focus on Cx43-based channels. We pointed out the contribution of connexins in neural cells populations during neurodegenerative processes to explore potential neuroprotective therapeutic applications.

Keywords: connexin; gap junction; hemichannel; neurodegeneration; neuroprotection.

Figure 1

Schematic representation of GJ intercellular communication (GJIC) and HC-mediated cell-to-extracellular environment communication. Cxs, composed by 4 transmembrane domains and an intracellular carboy-tail, are organized to homomeric or heteromeric HCs. GJ plaques are structures of hundreds up to thousands of single channels, which mediate exchanges of small molecules, substrates and metabolites. Those structures show free HCs exposed to the plaque border, where each cell adds newly synthetized HCs. These structures are crucial players of the GJIC and HCs-mediated cell-to-extracellular environment communication and lead to the information exchanges between neighboring cells favoring synchronized and concerted responses. Cx, connexin; HC, hemichannel; GJ, gap junction.