Gedeon Richter Plc., Pharmacology and Drug Safety Department, Budapest, Gyömrői u, 19-21, Hungary.
Brain Res Bull. 2013 Apr;93:86-96. doi: 10.1016/j.brainresbull.2012.11.003. Epub 2012 Nov 20.
The precise role of nicotinic acetylcholine receptors (nAChRs) in central cognitive processes still remains incompletely understood almost 150 years after its initial discovery. Central nAChRs are activated by acetylcholine, which functions in the extracellular space as a nonsynaptic messenger. Recently, a novel concept in the nAChR mode of operation has been described as a fast-type nonsynaptic transmission. In this review, we attempt to summarise the experimental findings that support the role of one of the most distributed receptor subtypes, the α7 nAChRs, and particularly focus on its procognitive effects following receptor activation. The basic characteristics of α7 nAChRs are discussed, from receptor homology to cellular-level functions. Synaptic plasticity is often implicated with α7 nAChRs on the basis of several diverse studies. Here, we provide a summary of the plastic features of the α7 receptor subtype and its role in higher level cognitive function. Finally, recent clinical evidence is reviewed, which demonstrates with increasing confidence the promise α7 nAChRs as a molecular target in future pharmacotherapy to prevent cognitive decline in various types of dementia, specifically, via the development of positive allosteric modulator compounds.
尼古丁型乙酰胆碱受体 (nAChRs) 在中枢认知过程中的精确作用,在其最初发现近 150 年后仍不完全清楚。中枢 nAChRs 被乙酰胆碱激活,乙酰胆碱在细胞外空间作为非突触信使发挥作用。最近,nAChR 作用模式的一个新概念被描述为快速型非突触传递。在这篇综述中,我们试图总结支持最广泛分布的受体亚型之一,即α7 nAChRs 的作用的实验发现,特别是特别关注其在受体激活后的认知促进作用。从受体同源性到细胞水平功能,讨论了α7 nAChRs 的基本特征。基于多项不同的研究,通常将突触可塑性与α7 nAChRs 联系在一起。在这里,我们总结了α7 受体亚型的可塑性特征及其在高级认知功能中的作用。最后,回顾了最近的临床证据,越来越有信心地证明α7 nAChRs 作为未来治疗各种类型痴呆症的药物治疗的分子靶点的前景,特别是通过开发正变构调节剂化合物来预防认知能力下降。