HiQScreen Sàrl, Geneva, Switzerland (D.B., F.M.); AbbVie Inc., North Chicago, Illinois (C-H.L.L., D.D-R.); and FORUM Pharmaceuticals Inc., Waltham, Massachusetts (D.F.)
HiQScreen Sàrl, Geneva, Switzerland (D.B., F.M.); AbbVie Inc., North Chicago, Illinois (C-H.L.L., D.D-R.); and FORUM Pharmaceuticals Inc., Waltham, Massachusetts (D.F.).
Pharmacol Rev. 2015 Oct;67(4):1025-73. doi: 10.1124/pr.113.008581.
Progress in the fields of neuroscience and molecular biology has identified the forebrain cholinergic system as being important in many higher order brain functions. Further analysis of the genes encoding the nicotinic acetylcholine receptors (nAChRs) has highlighted, in particular, the role of α7 nAChRs in these higher order brain functions as evidenced by their peculiar physiologic and pharmacological properties. As this receptor has gained the attention of scientists from academia and industry, our knowledge of its roles in various brain and bodily functions has increased immensely. We have also seen the development of small molecules that have further refined our understanding of the roles of α7 nAChRs, and these molecules have begun to be tested in clinical trials for several indications. Although a large body of data has confirmed a role of α7 nAChRs in cognition, the translation of small molecules affecting α7 nAChRs into therapeutics has to date only progressed to the stage of testing in clinical trials. Notably, however, most recent human genetic and biochemical studies are further underscoring the crucial role of α7 nAChRs and associated genes in multiple organ systems and disease states. The aim of this review is to discuss our current knowledge of α7 nAChRs and their relevance as a target in specific functional systems and disease states.
神经科学和分子生物学领域的进展表明，前脑胆碱能系统在许多高级脑功能中起着重要作用。对编码烟碱型乙酰胆碱受体（nAChRs）的基因的进一步分析特别强调了α7 nAChRs 在这些高级脑功能中的作用，这一点可以从其独特的生理和药理学特性得到证明。由于该受体引起了学术界和工业界科学家的关注，我们对其在各种脑和身体功能中的作用的了解大大增加。我们还看到了小分子的发展，这些小分子进一步深化了我们对α7 nAChRs 作用的理解，这些分子已经开始在几种适应症的临床试验中进行测试。尽管大量数据证实了α7 nAChRs 在认知中的作用，但影响α7 nAChRs 的小分子药物的转化迄今为止仅进展到临床试验测试阶段。然而，值得注意的是，最近的人类遗传和生化研究进一步强调了α7 nAChRs 及其相关基因在多个器官系统和疾病状态中的关键作用。本文的目的是讨论我们目前对α7 nAChRs 的认识及其作为特定功能系统和疾病状态靶点的相关性。
