Mechanism of signal transduction and receptor activation in ligand gated ion channel receptors

该项目寻求提供有关神经递质受体的基本新信息，神经递质受体介导快速突触神经传递。这一知识很重要，因为配体门控离子通道受体的Cys-loop家族负责广泛的神经元信号传递以及兴奋性和抑制性受体的控制。Cys-loop受体受两种治疗药物(例如，苯二氮卓类、巴比妥类、止吐药)和娱乐用药物(如。酒精、尼古丁)。它们也是开发新的治疗药物的目标，例如用于增强记忆的nAChR变构调节剂，或调节GlyR以缓解痉挛或慢性疼痛。该项目将利用该实验室和其他实验室取得的一系列分子进展来阐明神经递质如何使其受体激活并发出信号。这一基本信息具有重大的医学意义，因为由配体门控离子通道受体突变引起的突触传递缺陷会导致许多神经和精神疾病状态。配体门控受体也是治疗药物的主要靶点，这项研究中获得的信息也可能为药物用于增强或抑制突触信号的新方法提供见解。

This project seeks to provide fundamental new information about the means by which neurotransmitter receptors, which mediate fast synaptic neurotransmission, operate. This knowledge is important since the Cys-loop family of ligand gated ion channel receptors are responsible for a wide range of neuronal signalling and the control of both excitatory and inhibitory receptors. The Cys-loop receptors are modulated by both therapeutic drugs (eg. benzodiazepines, barbiturates, antiemetics) and by recreational drugs (eg. alcohol, nicotine). They are also targets for development of new therapeutic drugs, such as allosteric modulators of nAChR for memory enhancement, or modulating GlyR to relieve spasticity or chronic pain. The project will use a range of molecular advances made by this and other laboratories to clarify how neurotransmitters enable their receptors to activate and signal. This fundamental information is of major medical significance as defective synaptic transmission, caused by mutations in ligand gated ion channel receptors, gives rise to a number of neurological and psychiatric disease states. The ligand gated receptors are also major targets for therapeutic drugs and the information gained in this study may also provide insights into new ways in which drugs could be used to enhance or inhibit synaptic signalling.