Jaremko William J, Huang Zhen, Wen Wei, Wu Andrew, Karl Nicholas, Niu Li
Department of Chemistry and Center for Neuroscience Research, University at Albany, SUNY, Albany, New York 12222, USA.
RNA Dis. 2017;4(2). Epub 2017 Jun 12.
AMPA and kainate receptors, along with NMDA receptors, are distinct subtypes of glutamate ion channels. Excessive activity of AMPA and kainate receptors has been implicated in neurological diseases, such as epilepsy and neuropathic pain. Antagonists that block their activities are therefore potential drug candidates. In a recent article in the by Jaremko . 2017, we have reported on the discovery and molecular characterization of an RNA aptamer of a dual functionality: the full-length RNA (101 nucleotide) inhibits AMPA receptors while the truncated or the short (55 nucleotide) RNA inhibits both the AMPA and kainate receptors. The full-length RNA aptamer was isolated through a specially designed, systematic evolution of ligands by exponential enrichment (SELEX) using only a single type of AMPA receptors expressed in HEK-293 cells. The design feature and the results of our recent article are highlighted here, as they demonstrate the utility of the SELEX approach and the potential of using a single AMPA receptor type to develop potent, novel RNA aptamers targeting multiple subunits and AMPA/kainate receptor subtypes with length-dependent functionalities.
AMPA受体、海人酸受体与NMDA受体一样,都是谷氨酸离子通道的不同亚型。AMPA受体和海人酸受体的过度激活与癫痫和神经性疼痛等神经系统疾病有关。因此,阻断其活性的拮抗剂是潜在的候选药物。在Jaremko等人于2017年发表在《》上的一篇近期文章中,我们报道了一种具有双重功能的RNA适配体的发现及其分子特征:全长RNA(101个核苷酸)抑制AMPA受体,而截短型或短链(55个核苷酸)RNA则同时抑制AMPA受体和海人酸受体。全长RNA适配体是通过一种专门设计的指数富集配体系统进化技术(SELEX)分离得到的,该技术仅使用在HEK-293细胞中表达的单一类型的AMPA受体。本文重点介绍了我们近期文章的设计特点和结果,因为它们展示了SELEX方法的实用性,以及利用单一类型的AMPA受体开发具有长度依赖性功能、靶向多个亚基和AMPA/海人酸受体亚型的强效新型RNA适配体的潜力。