Donaldson Lucy F, Beazley-Long Nicholas
School of Life Sciences and Arthritis Research UK Pain Centre, University of Nottingham, Nottingham NG7 2UH, UK.
School of Life Sciences and Arthritis Research UK Pain Centre, University of Nottingham, Nottingham NG7 2UH, UK.
Drug Discov Today. 2016 Nov;21(11):1787-1798. doi: 10.1016/j.drudis.2016.06.017. Epub 2016 Jun 18.
Since the sequencing of metazoan genomes began, it has become clear that the number of expressed proteins far exceeds the number of genes. It is now estimated that more than 98% of human genes give rise to multiple proteins through alternative pre-mRNA splicing. In this review, we highlight the known alternative splice variants of many channels, receptors, and growth factors that are important in nociception and pain. Recently, pharmacological control of alternative splicing has been proposed as potential therapy in cancer, wet age-related macular degeneration, retroviral infections, and pain. Thus, we also consider the effects that known splice variants of molecules key to nociception/pain have on nociceptive processing and/or analgesic action, and the potential for control of alternative pre-mRNA splicing as a novel analgesic strategy.
自从后生动物基因组测序开始以来，很明显，表达的蛋白质数量远远超过基因数量。现在估计，超过98%的人类基因通过可变前体mRNA剪接产生多种蛋白质。在这篇综述中，我们重点介绍了许多在伤害感受和疼痛中起重要作用的通道、受体和生长因子的已知可变剪接变体。最近，可变剪接的药理学控制已被提议作为癌症、湿性年龄相关性黄斑变性、逆转录病毒感染和疼痛的潜在治疗方法。因此，我们还考虑了伤害感受/疼痛关键分子的已知剪接变体对伤害性处理和/或镇痛作用的影响，以及将可变前体mRNA剪接控制作为一种新型镇痛策略的潜力。
