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
[1]   Dipeptidyl peptidase I activates neutrophil-derived serine proteases and regulates the development of acute experimental arthritis [J].
Adkison, AM ;
Raptis, SZ ;
Kelley, DG ;
Pham, CTN .
JOURNAL OF CLINICAL INVESTIGATION, 2002, 109 (03) :363-371
[2]   Surface cathepsin B protects cytotoxic lymphocytes from self-destruction after degranulation [J].
Balaji, KN ;
Schaschke, N ;
Machleidt, W ;
Catalfamo, M ;
Henkart, PA .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (04) :493-503
[3]  
Beck H, 2001, EUR J IMMUNOL, V31, P3726, DOI 10.1002/1521-4141(200112)31:12<3726::AID-IMMU3726>3.0.CO
[4]  
2-O
[5]   Lysosomal cysteine proteases in the lung:: role in protein processing and immunoregulation [J].
Bühling, F ;
Waldburg, N ;
Reisenauer, A ;
Heimburg, A ;
Golpon, H ;
Welte, T .
EUROPEAN RESPIRATORY JOURNAL, 2004, 23 (04) :620-628
[6]   Nanoscale polymer carriers to deliver chemotherapeutic agents to tumours [J].
Cegnar, M ;
Kristl, J ;
Kos, J .
EXPERT OPINION ON BIOLOGICAL THERAPY, 2005, 5 (12) :1557-1569
[7]   Endosomal proteases in antigen presentation [J].
Chapman, HA .
CURRENT OPINION IN IMMUNOLOGY, 2006, 18 (01) :78-84
[8]   Emerging roles for cysteine proteases in human biology [J].
Chapman, HA ;
Riese, RJ ;
Shi, GP .
ANNUAL REVIEW OF PHYSIOLOGY, 1997, 59 :63-88
[9]   Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain [J].
Clark, Anna K. ;
Yip, Ping K. ;
Grist, John ;
Gentry, Clive ;
Staniland, Amelia A. ;
Marchand, Fabien ;
Dehvari, Maliheh ;
Wotherspoon, Glen ;
Winter, Janet ;
Ullah, Jakir ;
Bevan, Stuart ;
Malcangio, Marzia .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (25) :10655-10660
[10]   An orally active reversible inhibitor of cathepsin S inhibits human trans vivo delayed-type hypersensitivity [J].
Desai, SN ;
White, DM ;
O'Shea, KM ;
Brown, ML ;
Cywin, CL ;
Spero, DM ;
Panzenbeck, MJ .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2006, 538 (1-3) :168-174