Thurmond Robin L, Sun Siquan, Karlsson Lars, Edwards James P
Johnson & Johnson Pharmaceutical Research & Development LLC, San Diego, CA 92121, USA.
Curr Opin Investig Drugs. 2005 May;6(5):473-82.
Cathepsin S is one of the major cysteine proteases, and is expressed in the lysosome of antigen presenting cells; primarily dendritic cells, B-cells and macrophages. Cathepsin S is most well known for its critical function in the proteolytic digestion of the invariant chain chaperone molecules, thus controlling antigen presentation to CD4+ T-cells by major histocompatibility complex (MHC) class II molecules or to NK1.1+ T-cells via CD1 molecules. Cathepsin S also appears to participate in direct processing of exogenous antigens for presentation by MHC class II to CD4+ T-cells, or in cross-presentation by MHC class I molecules to CD8+ T-cells. In addition, although direct evidence is still lacking, in its secreted form cathepsin S is implicated in degradation of the extracellular matrix, which may contribute to the pathology of a number of diseases, including arthritis, atherosclerosis and chronic obstructive pulmonary disease. Therefore, inhibition of cathepsin S is a promising target for the development of novel therapeutics for a variety of indications.
组织蛋白酶S是主要的半胱氨酸蛋白酶之一，在抗原呈递细胞的溶酶体中表达，主要是树突状细胞、B细胞和巨噬细胞。组织蛋白酶S最为人所知的是其在恒定链伴侣分子的蛋白水解消化中的关键作用，从而通过主要组织相容性复合体（MHC）II类分子控制抗原呈递给CD4 + T细胞，或通过CD1分子控制抗原呈递给NK1.1 + T细胞。组织蛋白酶S似乎还参与外源性抗原的直接加工，以便由MHC II类分子呈递给CD4 + T细胞，或参与由MHC I类分子交叉呈递给CD8 + T细胞。此外，虽然仍缺乏直接证据，但组织蛋白酶S的分泌形式与细胞外基质的降解有关，这可能导致包括关节炎、动脉粥样硬化和慢性阻塞性肺疾病在内的多种疾病的病理过程。因此，抑制组织蛋白酶S是开发针对多种适应症的新型疗法的一个有前景的靶点。
