英国阿伯丁大学12月21日发布新闻公告称，该校科学家经过5年研究，终于找到了疼痛基因substance-P基因的开关，并发现辣椒素可刺激其开启。这一发现不仅有助于增进科学家对疼痛背后所隐含的遗传机制的理解，也有助于开发新的疼痛治疗药物和方法。相关研究成果发表在近期的《神经信号》杂志上。
Substance-P是位于感觉神经细胞中的一种疼痛基因，被认为与慢性炎症引起的疼痛有关。这种基因是惰性的，需要激活因子刺激才可进行充分表达。
为找到substance-P的基因开关，阿伯丁大学的研究人员花费了5年时间，并开发出一种寻找基因开关的新技术。他们通过比较人类、老鼠和鸡的基因序列，找到了一段长久以来一直保持不变的DNA片段。经研究，这段DNA就是可以打开感觉神经细胞中substance-P基因的强化因子序列，也就是substance-P基因开关。
研究人员还发现，辣椒素可刺激substance-P基因开关开启。辣椒素是辣椒中的一种活性成分，在其触碰到人类体表时会产生灼热感，有不少人将其用于慢性疼痛的治疗。
研究论文作者之一、阿伯丁大学的鲁思·罗斯教授指出，了解引发炎性疼痛的遗传过程，对于开发新的疼痛治疗方法十分必要。substance-P强化因子序列的发现，及其对辣椒素的反应，使得科学家对炎性疼痛的理解认识更进了一步。
该研究项目领导人阿拉斯代尔·麦肯齐博士则指出，88%的遗传疾病，如关节炎、肥胖症、抑郁症、心脏疾病和痴呆症等，可能会由基因开关缺陷引起，而非患者的基因缺陷造成。因此，发现substance-P基因开关，找出其作用机制，可大大加速以这些开关为标靶的新药开发。（生物谷Bioon.com）
生物谷推荐原文出处：
Neurosignals DOI: 10.1159/000322010
Long-Range Regulatory Synergy Is Required to Allow Control of the TAC1 Locus by MEK/ERK Signalling in Sensory Neurones
Lynne Shanleya Scott Davidsona Marissa Leara Anil Kumar Thotakurab Iain Joseph McEwana Ruth A. Rossa Alasdair MacKenzie
Abstract
Changes in the expression of the neuropeptide substance P(SP) in different populations of sensory neurones are associated with the progression of chronic inflammatory disease.Thus, understanding the genomic and cellular mechanisms driving the expression of the TAC1 gene, which encodes SP,in sensory neurones is essential to understanding its role in inflammatory disease. We used a novel combination of computational genomics, primary-cell culture and mouse transgenics to determine the genomic and cellular mechanisms that control the expression of TAC1 in sensory neurones. Intriguingly, we demonstrated that the promoter of the TAC1 gene must act in synergy with a remote enhancer, identified using comparative genomics, to respond to MAPK signalling that modulates the expression of TAC1 in sensory neurones.We also reveal that noxious stimulation of sensory neurones triggers this synergy in larger diameter sensory neurones –
an expression of SP associated with hyperalgesia. This noxious stimulation of TAC1 enhancer-promotor synergy could be strongly blocked by antagonism of the MEK pathway. This study provides a unique insight into the role of long-range enhancer-promoter synergy and selectivity in the tissuespecific response of promoters to specific signal transduction pathways and suggests a possible new avenue for the development of novel anti-inflammatory therapies.
