New Model for Nicotinic Acetylcholine Receptors
Signal transduction within and between cells mean that they can communicate important information and act upon it. Aberrant signal transduction is the cause of many of the most personally and financially devastating diseases including cancer, inflammatory diseases, cardiovascular disease and neuropsychiatric disease. Ligand-Gated Ion Channels are a major player in intercellular signal transduction. They are composed of transmembrane proteins that can exist under different conformations, at least one forming a pore through the membrane connecting the two neighbor compartments. The equilibrium between the various conformations is affected by the binding of ligands on the channels. The receptors of the cys-loop superfamily include the receptors for major neurotransmitters such as acetylcholine, serotonin, glycine, GABA, glutamate and histamine, and for Zn2+ ions. They play a central role in fast synaptic signaling in animal nervous systems. Dr. Jorgensen and colleagues have discovered two new receptor subunits of the cys-loop superfamily in C. elegans that are activated by protons acting as a transmitter. This marks the first time protons have been shown to be sufficient to activate the receptor complex
The mammalian nicotinic acetylcholine receptor is the target for potential therapeutic agents for diverse neurological disorders such as Alzheimer's and Parkinson's diseases, cognitive dysfunction, schizophrenia, depression, epilepsy, attention-deficit hyperactivity, Tourette's syndrome, and anxiety. In 2002 North American sales of anti psychotics approached $6 billion with an annual growth rate approaching 30%.
Stage of Development
PCT and US patent applications have been filed with the US Patent and Trademark Office and are pending. These technologies are available for developmental research support and licensing under either exclusive or non-exclusive terms.
Asim Beg, Paola Nix, Erik Jorgensen
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