Peptide and Protein Neurotoxin Toolbox in Research on Nicotinic Acetylcholine Receptors

The chapter briefly covers the history of protein and peptide neurotoxins in research on nicotinic acetylcholine receptors (nAChR). It all started with a great help of α-bungarotoxin and other similar α-neurotoxins from snake venoms in isolation from the Torpedo ray electric organ of the muscle-type nAChR as a first individual membrane receptor. The next contribu‐ tion of α-neurotoxins was the discovery with their aid of the first neuronal nAChR in the brain now known as homooligomeric α7 nAChR. An overview of various α-neurotoxins (so-called three-finger toxins) is presented below showing the structural differences between them, as well as the benefits of their current application for identification and quantification of different nAChR subtypes at normal state and at various pathologies such as Alzheimer’s and Parkin‐ son’s diseases, psychiatric diseases and nicotine addiction. A special emphasis is placed on the work at our institute, starting with the first detection of nAChRs as targets for the so-called weak or “non-conventional” neurotoxins. Recently, in proteomic studies of snake venoms, novel structural types have been discovered, such as covalently connected dimeric α-cobra‐ toxin or, on the contrary azemiopsin, the first peptide from venoms which does not contain disulfide bonds but still blocks selectively the muscle-type nAChR.