Murphy G, Lee M H
Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Box 139, Hills Road, Cambridge CB2 2XY, UK.
Ann Rheum Dis. 2005 Nov;64 Suppl 4(Suppl 4):iv44-7. doi: 10.1136/ard.2005.042465.
A role for metalloproteinases in the pathological destruction in diseases such as rheumatoid arthritis and osteoarthritis, and the irreversible nature of the ensuing cartilage and bone damage, have been the focus of much investigation for several decades. This has led to the development of broad spectrum metalloproteinase inhibitors as potential therapeutics. More recently it has been appreciated that several families of zinc dependent proteinases play significant and varied roles in the biology of the resident cells in these tissues, orchestrating development, remodelling, and subsequent pathological processes. They also play key roles in the activity of inflammatory cells. The task of elucidating the precise role of individual metalloproteinases is therefore a burgeoning necessity for the final design of metalloproteinase inhibitors if they are to be employed as therapeutic agents.
几十年来,金属蛋白酶在类风湿性关节炎和骨关节炎等疾病的病理破坏中的作用,以及随之而来的软骨和骨损伤的不可逆性,一直是大量研究的焦点。这促使人们开发广谱金属蛋白酶抑制剂作为潜在的治疗药物。最近人们认识到,几个锌依赖性蛋白酶家族在这些组织中驻留细胞的生物学过程中发挥着重要且多样的作用,协调着发育、重塑以及随后的病理过程。它们在炎症细胞的活性中也起着关键作用。因此,如果要将金属蛋白酶抑制剂用作治疗药物,阐明单个金属蛋白酶的确切作用对于其最终设计来说是一项迫切的必要任务。