Nicotinic acetylcholine receptors nicotinic receptor molecular chaperones and mechanisms of insecticide action

本研究计划的重点是一类重要的神经递质受体，烟碱乙酰胆碱受体（nAChRs），它是两类主要杀虫剂（新烟碱和spinosad）的靶点。与几乎所有种类的杀虫剂一样，目前在田间昆虫种群中出现了抗药性的主要问题。本研究计划的重点是阐明spinosad的作用机制，并探讨对该杀虫剂的抗性机制。与此同时，将进行研究，以调查蛋白质在产生功能性nachr中的作用。该研究项目第二个方面的目标是促进旨在阐明昆虫nachr药理多样性的研究。昆虫nachr与脊椎动物神经系统中表达的nachr密切相关。人类的这种受体与阿尔茨海默病和精神分裂症等疾病有关。事实上，本申请中提出的一些研究将集中在哺乳动物的nachr上，预计从长远来看，这些研究结果可能与旨在发现针对人类nachr的药物的研究相关。

The focus of this research proposal is an important class of neurotransmitter receptor, the nicotinic acetylcholine receptors (nAChRs), which are target sites for two major classes of insecticide (neonicotinoids and spinosad). As with almost all classes of insecticides, major problems of resistance have now developed in insect field populations. A particular emphasis of this research proposal is to elucidate the mechanism of action of spinosad and to explore mechanisms of resistance to this insecticide. In parallel, studies will be undertaken to investigate the role of proteins involved in generating functional nAChRs. A goal of this second aspect of the proposed research project is to facilitate research aimed at elucidating the pharmacological diversity of insect nAChRs. Insect nAChRs are closely related to nAChRs expressed in the nervous system of vertebrates. Such receptors in humans have been implicated in disorders such as Alzheimer's disease and schizophrenia. Indeed, some of the research proposed in this application will focus on mammalian nAChRs and it is expected that the research findings may, in the longer term, have relevance to research aimed at discovery of drugs targeting human nAChRs.