The role of cathepsins in osteoporosis and arthritis: rationale for the design of new therapeutics.
The role of cathepsins in osteoporosis and arthritis: rationale for the design of new therapeutics.
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DOI：
10.1016/j.addr.2004.12.013
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发表时间：
2005-05
影响因子：
16.1
通讯作者：
Y. Yasuda;J. Kaleta;D. Brömme
中科院分区：
文献类型：
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作者：
Y. Yasuda;J. Kaleta;D. Brömme
木瓜蛋白酶家族的人半胱氨酸蛋白酶已被认为是肌肉骨骼疾病的潜在药物靶点。大多数的兴趣集中在组织蛋白酶S和K，其在免疫系统的细胞和能够有效降解细胞外基质蛋白，特别是胶原蛋白的细胞中显示选择性表达。组织蛋白酶K在破骨细胞中的主要表达使该酶成为开发骨质疏松症新型抗吸收药物的主要靶点，而组织蛋白酶S似乎是包括类风湿性关节炎在内的各种炎症性疾病的有吸引力的药物靶点候选者。由于类风湿性关节炎同时是一种炎症性和关节破坏性疾病，因此联合抑制组织蛋白酶S和K应该是有益的。本文综述了靶向组织蛋白酶在关节炎和骨质疏松症中的作用原理和最新进展。
Human cysteine proteases of the papain family have been recognized as potential drug targets for musculoskeletal diseases. Most of the interest is focused on cathepsins S and K, which display selective expression in cells of the immune system and cells capable to efficiently degrade extracellular matrix proteins, in particular collagens. The predominant expression of cathepsin K in osteoclasts has rendered the enzyme into a major target for the development of novel anti-resorptive drugs in osteoporosis whereas cathepsin S appears to be an attractive drug target candidate for various inflammatory diseases including rheumatoid arthritis. Since rheumatoid arthritis is at the same time an inflammatory and joint destructive disorder, the combined inhibition of both cathepsins S and K should be beneficial. This review will outline the rationale and recent progress for targeting cathepsins in arthritis and osteoporosis.