α-Conotoxins to explore the molecular, physiological and pathophysiological functions of neuronal nicotinic acetylcholine receptors

The vast diversity of neuronal nicotinic acetylcholine subunits expressed in the central and peripheral nervous systems, as well as in non-neuronal tissues, constitutes a formidable challenge for researchers and clinicians to decipher the role of particular subtypes, including complex subunit associations, in physiological and pathophysiological functions. Many natural products target the nAChRs, but there is no richer source of nicotinic ligands than the venom of predatory gastropods known as cone snails. Indeed, every single species of cone snail was shown to produce at least one type of such α-conotoxins. These tiny peptides (10-25 amino acids), constrained by disulfide bridges, proved to be unvaluable tools to investigate the structure and function of nAChRs, some of them having also therapeutic potential. In this review, we provide a recent update on the pharmacology and subtype specificity of several major α-conotoxins.