英國(guó)阿伯丁大學(xué)12月21日發(fā)布新聞公告稱,，該校科學(xué)家經(jīng)過(guò)5年研究,，終于找到了疼痛基因substance-P基因的開(kāi)關(guān),，并發(fā)現(xiàn)辣椒素可刺激其開(kāi)啟。這一發(fā)現(xiàn)不僅有助于增進(jìn)科學(xué)家對(duì)疼痛背后所隱含的遺傳機(jī)制的理解,，也有助于開(kāi)發(fā)新的疼痛治療藥物和方法。相關(guān)研究成果發(fā)表在近期的《神經(jīng)信號(hào)》雜志上,。
Substance-P是位于感覺(jué)神經(jīng)細(xì)胞中的一種疼痛基因,，被認(rèn)為與慢性炎癥引起的疼痛有關(guān)。這種基因是惰性的,，需要激活因子刺激才可進(jìn)行充分表達(dá),。
為找到substance-P的基因開(kāi)關(guān)，阿伯丁大學(xué)的研究人員花費(fèi)了5年時(shí)間,，并開(kāi)發(fā)出一種尋找基因開(kāi)關(guān)的新技術(shù),。他們通過(guò)比較人類、老鼠和雞的基因序列,，找到了一段長(zhǎng)久以來(lái)一直保持不變的DNA片段,。經(jīng)研究，這段DNA就是可以打開(kāi)感覺(jué)神經(jīng)細(xì)胞中substance-P基因的強(qiáng)化因子序列,，也就是substance-P基因開(kāi)關(guān),。
研究人員還發(fā)現(xiàn)，辣椒素可刺激substance-P基因開(kāi)關(guān)開(kāi)啟,。辣椒素是辣椒中的一種活性成分,，在其觸碰到人類體表時(shí)會(huì)產(chǎn)生灼熱感，有不少人將其用于慢性疼痛的治療,。
研究論文作者之一,、阿伯丁大學(xué)的魯思·羅斯教授指出，了解引發(fā)炎性疼痛的遺傳過(guò)程,，對(duì)于開(kāi)發(fā)新的疼痛治療方法十分必要,。substance-P強(qiáng)化因子序列的發(fā)現(xiàn)，及其對(duì)辣椒素的反應(yīng),，使得科學(xué)家對(duì)炎性疼痛的理解認(rèn)識(shí)更進(jìn)了一步,。
該研究項(xiàng)目領(lǐng)導(dǎo)人阿拉斯代爾·麥肯齊博士則指出，88%的遺傳疾病,，如關(guān)節(jié)炎,、肥胖癥、抑郁癥,、心臟疾病和癡呆癥等,，可能會(huì)由基因開(kāi)關(guān)缺陷引起,，而非患者的基因缺陷造成。因此,，發(fā)現(xiàn)substance-P基因開(kāi)關(guān),，找出其作用機(jī)制，可大大加速以這些開(kāi)關(guān)為標(biāo)靶的新藥開(kāi)發(fā),。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
