Ghazal Pasha
COMSATS Institute of Information Technology, Islamabad, Pakistan.
Curr Protein Pept Sci. 2016;17(4):380-97. doi: 10.2174/1389203717666151218150704.
In 2004, Neuropeptide S (NPS) was identified to be the cognate ligand of the previously discovered orphan receptor GPCR 154, now termed as NPS receptor (NPSR). Since, then a wealth of data has elucidated the unique behavioral profile of this peptidergic system in numerous physiological function such as being pro-arousal and anxiolytic at the same time. Besides, its robust anxiolytic profile, this peptide system has been found to activate HPA axis and concomitant release of ACTH and corticosterone. Additionally, the involvement of NPS in reinstatement of drug seeking behavior has also been reported. In recent years, accumulating data from various labs have demonstrated an A/T single-nucleotide polymorphism (SNP) resulting in (Asn107Ile) switch in the human NPSR gene as the risk factor for various psychiatric disorders such as panic disorder, post traumatic syndrome, alcohol use disorders and enhanced anxiety sensitivity, although, this is in stark contrast to the findings made in animal models which have consistently projected the anxiolytic nature of this peptide system. Therefore, in context of robust involvement of NPS system in various psychiatric disorders this review article considers the importance of NPS from translational point of view and appraises the need of therapies to be tailored around NPSR. In this respect, pharmacology of important NPSR ligands which have been recently developed has been discussed together with their possible side effects profile. Additionally, this review article encompasses all recent developments in the field of NPS system highlighting the role of this neuropeptide in all those biological functions which are modulated by this system. The role of this peptide has been discussed in detail in the perspective of sleep regulation, anxiety, fear expression and most importantly in drug addiction. Additionally, neuroimaging and genetic linkage studies addressing the functional impact of NPSR1 variants in the aforementioned psychiatric disorders have also been discussed.
2004年，神经肽S（NPS）被确定为先前发现的孤儿受体GPCR 154（现称为NPS受体，NPSR）的同源配体。从那时起，大量数据阐明了这个肽能系统在众多生理功能中的独特行为特征，比如它同时具有促觉醒和抗焦虑作用。此外，除了强大的抗焦虑作用外，还发现这个肽系统能激活下丘脑-垂体-肾上腺（HPA）轴，并伴随促肾上腺皮质激素（ACTH）和皮质酮的释放。此外，也有报道称NPS参与了觅药行为的恢复。近年来，来自各个实验室的越来越多的数据表明，人类NPSR基因中一个A/T单核苷酸多态性（SNP）导致（Asn107Ile）转换，是多种精神疾病的危险因素，如惊恐障碍、创伤后综合征、酒精使用障碍和焦虑敏感性增强，尽管这与动物模型中的发现形成了鲜明对比，动物模型一直显示这个肽系统具有抗焦虑特性。因此，鉴于NPS系统在各种精神疾病中的重要作用，这篇综述文章从转化的角度考虑了NPS的重要性，并评估了围绕NPSR定制治疗方法的必要性。在这方面，讨论了最近开发的重要NPSR配体的药理学及其可能的副作用。此外，这篇综述文章涵盖了NPS系统领域的所有最新进展，突出了这种神经肽在该系统调节的所有生物功能中的作用。从睡眠调节、焦虑、恐惧表达以及最重要的药物成瘾等角度详细讨论了这种肽的作用。此外，还讨论了针对NPSR1变体在上述精神疾病中的功能影响的神经影像学和基因连锁研究。
