Lynx1 prototoxins: critical accessory proteins of neuronal nicotinic acetylcholine receptors

Abstract

Nicotinic receptors of the cholinergic system are ligand-gated ion channels, responding to the excitatory neurotransmitter, acetylcholine, and the addictive component of tobacco, nicotine. They help to transduce salient information in the environment by activating specific neural circuitry in normal and disease states. While nicotinic receptors are promising neurological and neuropsychiatric disorder targets, they have fallen out of favor after several late-stage clinical failures. Targeting the complex of the nicotinic receptor, including lynx1 accessory proteins, could be the key to unlocking the intractable nAChR for therapeutic development. Lynx1 binds to the extracellular face of the nAChR and acts as a critical modulator, suppressing memory, learning, and plasticity. Lynx1 removal in animal models leads to memory and plasticity enhancements, some of which have therapeutic relevance for neuropsychiatric and neurological disease. A review of the lynx1 accessory modulator and its role in modulating neuronal nAChRs will be discussed.