Cysteine cathepsin S as an immunomodulatory target: present and future trends

被引:90
作者
Gupta, Suman [1 ]
Singh, Rakesh Kumar [1 ]
Dastidar, Sunanda [1 ]
Ray, Abhijit [1 ]
机构
[1] Ranbaxy Res Labs, Dept Pharmacol, New Drug Discovery Res, Gurgaon 1220015, Haryana, India
关键词
autoimmune disorders; cathepsin; cysteine protease; inhibitors;
D O I
10.1517/14728222.12.3.291
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Objective: Antigen presentation is the key to immune response. Cathepsin S plays a major role in the degradation of the invariant peptide chain associated with the major histocompatibility complex and thus affects antigen presentation. This review will focus on the recent developments made in field of cysteine cathepsins especially cathepsin S and their future prospects as a therapeutic target. Methods: Selective cathepsin inhibitors for targeting autoimmune disorders, atherosclerosis, osteoporosis, osteoarthritis and cancer are being pursued by many pharmaceutical companies. Recent publications in this field have been used as references to evaluate the current and future trends in cathepsin S inhibitors as an immunomodulatory target. Conclusions: The temporal and spatial position occupied by cathepsin S in immune presentation, gives rise to the hope that an inhibitor would impart selectivity with a lesser propensity for side effects than other immunosuppressive agents.
引用
收藏
页码:291 / 299
页数:9
相关论文
共 67 条
[41]   Regulation of elastinolytic cysteine proteinase activity in normal and cathepsin K-deficient human macrophages [J].
Punturieri, A ;
Filippov, S ;
Allen, E ;
Caras, I ;
Murray, R ;
Reddy, V ;
Weiss, SJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (06) :789-799
[42]  
Rao NV, 1997, J BIOL CHEM, V272, P10260
[43]   The lysosomal cysteine protease cathepsin L regulates keratinocyte proliferation by control of growth factor recycling [J].
Reinheckel, T ;
Hagemann, S ;
Dollwet-Mack, S ;
Martinez, E ;
Lohmüller, T ;
Zlatkovic, G ;
Tobin, DJ ;
Maas-Szabowski, N ;
Peters, C .
JOURNAL OF CELL SCIENCE, 2005, 118 (15) :3387-3395
[44]   Cathepsin S activity regulates antigen presentation and immunity [J].
Riese, RJ ;
Mitchell, RN ;
Villadangos, JA ;
Shi, GP ;
Palmer, JT ;
Karp, ER ;
De Sanctis, GT ;
Ploegh, HL ;
Chapman, HA .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (11) :2351-2363
[45]   Cathepsin L deficiency as molecular defect of furless:: hyperproliferation of keratinocytes and pertubation of hair follicle cycling [J].
Roth, W ;
Deussing, J ;
Botchkarev, VA ;
Pauly-Evers, M ;
Saftig, P ;
Hafner, A ;
Schmidt, P ;
Schmahl, W ;
Scherer, J ;
Anton-Lamprecht, I ;
Von Figura, K ;
Paus, R ;
Peters, C .
FASEB JOURNAL, 2000, 14 (13) :2075-2086
[46]   Specificity of human cathepsin S determined by processing of peptide substrates and MHC class II-associated invariant chain [J].
Rueckrich, Thomas ;
Brandenburg, Jens ;
Cansier, Alexander ;
Mueller, Margret ;
Stevanovic, Stefan ;
Schilling, Klaus ;
Wiederanders, Bernd ;
Beck, Alexander ;
Melms, Arthur ;
Reich, Michael ;
Driessen, Christoph ;
Kalbacher, Hubert .
BIOLOGICAL CHEMISTRY, 2006, 387 (10-11) :1503-1511
[47]   Role for cathepsin F in invariant chain processing and major histocompatibility complex class II peptide loading by macrophages [J].
Shi, GP ;
Bryant, RAR ;
Riese, R ;
Verhelst, S ;
Driessen, C ;
Li, ZQ ;
Bromme, D ;
Ploegh, HL ;
Chapman, HA .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (07) :1177-1185
[48]   Deficiency of the cysteine protease cathepsin S impairs microvessel growth [J].
Shi, GP ;
Sukhova, GK ;
Kuzuya, M ;
Ye, Q ;
Du, J ;
Zhang, Y ;
Pan, JH ;
Lu, ML ;
Cheng, XW ;
Iguchi, A ;
Perrey, S ;
Lee, AME ;
Chapman, HA ;
Libby, P .
CIRCULATION RESEARCH, 2003, 92 (05) :493-500
[49]   Cathepsin S required for normal MHC class II peptide loading and germinal center development [J].
Shi, GP ;
Villadangos, JA ;
Dranoff, G ;
Small, C ;
Gu, LJ ;
Haley, KJ ;
Riese, R ;
Ploegh, HL ;
Chapman, HA .
IMMUNITY, 1999, 10 (02) :197-206
[50]   Cystatin C deficiency in human atherosclerosis and aortic aneurysms [J].
Shi, GP ;
Sukhova, GK ;
Grubb, A ;
Ducharme, A ;
Rhode, LH ;
Lee, RT ;
Ridker, PM ;
Libby, P ;
Chapman, HA .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 104 (09) :1191-1197