科学家在遗传学和药物学方面都找到了新证据，证明一种名为胶原酶-2的蛋白质在多发性硬化症(MS)的产生中具有一定作用，这项发现为战胜这种令人虚弱的疾病提供了一条新途径。相关论文4月4日发表在《生物化学杂志》（Journal of Biological Chemistry）上。
胶原酶-2属于一个名为基质金属蛋白酶（MMPs，胶原酶-2是MMP8）的蛋白质家族，它们是分解胶原和身体中其他结缔组织成分的一大酶类。MMPs因为能降解维持血脑屏障的组织，使一些多余的细胞侵入并破坏神经，所以被认为与MS相关。实际上，研究人员在患病个体的血液和脑脊液中发现，MMPs的数量都有提高。
Carlos Lopez-Otin及其同事们利用MS小鼠模型对MMP8进行了两项研究，分析它们和这种疾病究竟有多大相关性。首先，他们开发出一种MMP8基因失效的突变小鼠，发现这种小鼠的大脑中入侵的多余细胞减少，被破坏的神经也很少，而且它们的临床状态也有总体提高。
他们还让MS患病小鼠服用一种能阻断MMP8活性的药物，发现这种方法也能减轻疾病的严重程度。总之，这些发现首次为MMP8引起MS提供了因果证据，并找到了一个新的治疗靶点。（来源：EurekAlert!中文版）
生物谷推荐原始出处：
（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.
