科學(xué)家在遺傳學(xué)和藥物學(xué)方面都找到了新證據(jù),，證明一種名為膠原酶-2的蛋白質(zhì)在多發(fā)性硬化癥(MS)的產(chǎn)生中具有一定作用,，這項(xiàng)發(fā)現(xiàn)為戰(zhàn)勝這種令人虛弱的疾病提供了一條新途徑。相關(guān)論文4月4日發(fā)表在《生物化學(xué)雜志》（Journal of Biological Chemistry）上,。
膠原酶-2屬于一個(gè)名為基質(zhì)金屬蛋白酶（MMPs,，膠原酶-2是MMP8）的蛋白質(zhì)家族，它們是分解膠原和身體中其他結(jié)締組織成分的一大酶類(lèi),。MMPs因?yàn)槟芙到饩S持血腦屏障的組織,，使一些多余的細(xì)胞侵入并破壞神經(jīng)，所以被認(rèn)為與MS相關(guān),。實(shí)際上,，研究人員在患病個(gè)體的血液和腦脊液中發(fā)現(xiàn)，MMPs的數(shù)量都有提高,。
Carlos Lopez-Otin及其同事們利用MS小鼠模型對(duì)MMP8進(jìn)行了兩項(xiàng)研究,，分析它們和這種疾病究竟有多大相關(guān)性。首先,，他們開(kāi)發(fā)出一種MMP8基因失效的突變小鼠,，發(fā)現(xiàn)這種小鼠的大腦中入侵的多余細(xì)胞減少，被破壞的神經(jīng)也很少,，而且它們的臨床狀態(tài)也有總體提高,。
他們還讓MS患病小鼠服用一種能阻斷MMP8活性的藥物，發(fā)現(xiàn)這種方法也能減輕疾病的嚴(yán)重程度,?？傊?，這些發(fā)現(xiàn)首次為MMP8引起MS提供了因果證據(jù)，并找到了一個(gè)新的治療靶點(diǎn),。（來(lái)源：EurekAlert!中文版）
生物谷推薦原始出處：
（Journal of Biological Chemistry）,，Vol. 283, Issue 14, 9465-9474，Alicia R. Folgueras,，Carlos López-Otín
Collagenase-2 Deficiency or Inhibition Impairs Experimental Autoimmune Encephalomyelitis in Mice*
Alicia R. Folgueras, Antonio Fueyo, Olivia García-Suárez¶, Jennifer Cox||, Aurora Astudillo¶, Paolo Tortorella**, Cristina Campestre, Ana Gutiérrez-Fernández, Miriam Fanjul-Fernández, Caroline J. Pennington, Dylan R. Edwards, Christopher M. Overall||, and Carlos López-Otín1
From the Departamento de Bioquímica y Biología Molecular, and Biología Funcional, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, and ¶Servicio de Anatomía Patológica, Hospital Central de Asturias, Oviedo 33006, Spain, the ||Departments of Oral Biological and Medical Sciences, and Biochemistry and Molecular Biology, Centre for Blood Research, University of British Columbia, Vancouver, V6T 1Z3 Canada, the **Dipartimento Farmaco-Chimico, Università degli Studi di Bari, Bari 70125, Italy, the Dipartimento di Scienze del Farmaco, Università G. d'Annunzio, Chieti 66013, Italy, and the School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ United Kingdom
Matrix metalloproteinases (MMPs) have been implicated in a variety of human diseases, including neuroimmunological disorders such as multiple sclerosis. However, the recent finding that some MMPs play paradoxical protective roles in these diseases has made necessary the detailed study of the specific function of each family member in their pathogenesis. To determine the relevance of collagenase-2 (MMP-8) in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, we have performed two different analyses involving genetic and biochemical approaches. First, we have analyzed the development of EAE in mutant mouse deficient in MMP-8, with the finding that the absence of this proteolytic enzyme is associated with a marked reduction in the clinical symptoms of EAE. We have also found that MMP-8-/- mice exhibit a marked reduction in central nervous system-infiltrating cells and demyelinating lesions. As a second approach, we have carried out a pharmacological inhibition of MMP-8 with a selective inhibitor against this protease (IC50 = 0.4 nM). These studies have revealed that the administration of the MMP-8 selective inhibitor to mice with EAE also reduces the severity of the disease. Based on these findings, we conclude that MMP-8 plays an important role in EAE development and propose that this enzyme may be a novel therapeutic target in human neuro-inflammatory diseases such as multiple sclerosis.
