Translational studies of group II metabotropic glutamate receptors (mGluR2, mGluR3) and their role in schizophrenia

目前用于治疗精神分裂症的所有药物都是通过阻断一种叫做多巴胺的大脑化学传递素的活动来起作用的。不幸的是，这些药物不是很有效，而且有很多副作用。最近的研究表明，另一种递质谷氨酸在精神分裂症中也很重要，对该系统起作用的药物可能会更好。谷氨酸通过与受体分子结合而起作用。其中一种亚型被称为II组代谢型谷氨酸受体（mGluRs），它们引起了极大的兴趣，因为去年一种作用于这些受体的药物被证明对治疗精神分裂症有效（而且没有主要副作用）——这是有史以来第一个成功治疗这种疾病的非多巴胺药物。我们已经在II组mGluRs上工作了好几年，这个应用程序寻求建立在我们现有的知识和专业知识的基础上，以发现更多关于这些受体如何工作的信息，从而帮助制造更好的精神分裂症药物。为了做到这一点，我们将使用遗传和分子方法，研究在没有这些受体的情况下脑细胞是如何工作的，并研究患有这种疾病的人大脑中的受体。根据这项资助计划，这项工作将与哈洛葛兰素史克公司的同事共同积极合作完成。

All current drugs used to treat schizophrenia work by blocking actions of a brain chemical transmitter called dopamine. Unfortunately these drugs are not very effective and have many side-effects. Recent research has suggested that another transmitter, glutamate, is also important in schizophrenia, and that drugs working on this system may be better. Glutamate acts by binding to molecules called receptors. One subtype of these is called group II metabotropic glutamate receptors (mGluRs), and these are of great interest because last year a drug which acts on these receptors was shown to be effective (and free of major side effects) in treatment of schizophrenia - the first ever non-dopamine drug to succeed in the illness. We have been working on group II mGluRs for several years, and this application seeks to build upon our existing knowledge and expertise to disover more about how these receptors work and so help make better drugs for schizophrenia. To do this, we will use genetic and molecular methods, investigate how brain cells work in the absence of these receptors, and study the receptors in the brains of people who had the illness. In line with this funding scheme, the work will be done jointly and in active collaboration with colleagues at GlaxoSmithKline in Harlow.