Caspases As Therapeutic Targets

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2008 Feb 27

PMID 18298652

Citations 33

Authors

B Howley

H O Fearnhead

Affiliations

Soon will be listed here.

Abstract

The development of small molecules to modulate caspase activity offers a novel therapeutic strategy in the treatment of apoptosis-related and inflammatory diseases. Caspases are key mediators of apoptosis and inflammation; deregulation of their activation or expression can lead to the development of conditions such as neurodegenerative and autoinflammatory disorders. This review details the different caspase-associated disorders while focusing on caspase-1 inhibition as a potential therapeutic strategy. Problems facing the development of effective and safe caspase therapeutics will also be addressed.

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References

Stehlik C, Krajewska M, Welsh K, Krajewski S, Godzik A, Reed J . The PAAD/PYRIN-only protein POP1/ASC2 is a modulator of ASC-mediated nuclear-factor-kappa B and pro-caspase-1 regulation. Biochem J. 2003; 373(Pt 1):101-13. PMC: 1223462. DOI: 10.1042/BJ20030304. View

Hilbert S, Luna R, Zhang J, Wang Y, Hopkins R, Yu Z . Allograft heart valves: the role of apoptosis-mediated cell loss. J Thorac Cardiovasc Surg. 1999; 117(3):454-62. DOI: 10.1016/s0022-5223(99)70324-7. View

Quadri S, Segall L, de Perrot M, Han B, Edwards V, Jones N . Caspase inhibition improves ischemia-reperfusion injury after lung transplantation. Am J Transplant. 2005; 5(2):292-9. DOI: 10.1111/j.1600-6143.2004.00701.x. View

Pockros P, Schiff E, Shiffman M, McHutchison J, Gish R, Afdhal N . Oral IDN-6556, an antiapoptotic caspase inhibitor, may lower aminotransferase activity in patients with chronic hepatitis C. Hepatology. 2007; 46(2):324-9. DOI: 10.1002/hep.21664. View

Chen M, Goel O, Hyun J, Magano J, Rubin J . An efficient stereoselective synthesis of [3S(1S,9S)]-3-[[[9-(benzoylamino) octahydro-6,10-dioxo-6H-pyridazino-(1,2-a)(1,2)-diazepin-1-yl]-carbonyl ]amino]-4-oxobutanoic acid, an interleukin converting enzyme (ICE) inhibitor. Bioorg Med Chem Lett. 1999; 9(11):1587-92. DOI: 10.1016/s0960-894x(99)00236-x. View

Liu X, Drognitz O, Neeff H, Benz S, Hopt U . Apoptosis is caused by prolonged organ preservation and blocked by apoptosis inhibitor in experimental rat pancreatic grafts. Transplant Proc. 2004; 36(4):1209-10. DOI: 10.1016/j.transproceed.2004.04.046. View

Hardy J, Lam J, Nguyen J, OBrien T, Wells J . Discovery of an allosteric site in the caspases. Proc Natl Acad Sci U S A. 2004; 101(34):12461-6. PMC: 514654. DOI: 10.1073/pnas.0404781101. View

Black R, Kronheim S, Merriam J, March C, Hopp T . A pre-aspartate-specific protease from human leukocytes that cleaves pro-interleukin-1 beta. J Biol Chem. 1989; 264(10):5323-6. View

Woo M, Hakem R, Furlonger C, Hakem A, Duncan G, Sasaki T . Caspase-3 regulates cell cycle in B cells: a consequence of substrate specificity. Nat Immunol. 2003; 4(10):1016-22. DOI: 10.1038/ni976. View

10.

Bruey J, Bruey-Sedano N, Newman R, Chandler S, Stehlik C, Reed J . PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages. J Biol Chem. 2004; 279(50):51897-907. DOI: 10.1074/jbc.M406741200. View

11.

Zermati Y, Garrido C, Amsellem S, Fishelson S, Bouscary D, Valensi F . Caspase activation is required for terminal erythroid differentiation. J Exp Med. 2001; 193(2):247-54. PMC: 2193347. DOI: 10.1084/jem.193.2.247. View

12.

Gu Y, Kuida K, Tsutsui H, Ku G, Hsiao K, Fleming M . Activation of interferon-gamma inducing factor mediated by interleukin-1beta converting enzyme. Science. 1997; 275(5297):206-9. DOI: 10.1126/science.275.5297.206. View

13.

Fischer S, Cassivi S, Xavier A, Cardella J, Cutz E, Edwards V . Cell death in human lung transplantation: apoptosis induction in human lungs during ischemia and after transplantation. Ann Surg. 2000; 231(3):424-31. PMC: 1421014. DOI: 10.1097/00000658-200003000-00016. View

14.

Eckhart L, Declercq W, Ban J, Rendl M, Lengauer B, Mayer C . Terminal differentiation of human keratinocytes and stratum corneum formation is associated with caspase-14 activation. J Invest Dermatol. 2000; 115(6):1148-51. DOI: 10.1046/j.1523-1747.2000.00205.x. View

15.

Stadelmann C, Deckwerth T, Srinivasan A, Bancher C, Bruck W, Jellinger K . Activation of caspase-3 in single neurons and autophagic granules of granulovacuolar degeneration in Alzheimer's disease. Evidence for apoptotic cell death. Am J Pathol. 1999; 155(5):1459-66. PMC: 1866960. DOI: 10.1016/S0002-9440(10)65460-0. View

16.

Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, Thompson C . Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol. 2004; 6(12):1221-8. DOI: 10.1038/ncb1192. View

17.

Carter B, Kornblau S, Tsao T, Wang R, Schober W, Milella M . Caspase-independent cell death in AML: caspase inhibition in vitro with pan-caspase inhibitors or in vivo by XIAP or Survivin does not affect cell survival or prognosis. Blood. 2003; 102(12):4179-86. DOI: 10.1182/blood-2003-03-0960. View

18.

Hara H, Friedlander R, Gagliardini V, Ayata C, Fink K, Huang Z . Inhibition of interleukin 1beta converting enzyme family proteases reduces ischemic and excitotoxic neuronal damage. Proc Natl Acad Sci U S A. 1997; 94(5):2007-12. PMC: 20033. DOI: 10.1073/pnas.94.5.2007. View

19.

Wang J, Chun H, Wong W, Spencer D, Lenardo M . Caspase-10 is an initiator caspase in death receptor signaling. Proc Natl Acad Sci U S A. 2001; 98(24):13884-8. PMC: 61136. DOI: 10.1073/pnas.241358198. View

20.

Liang Q, Liou A, Ding Y, Cao G, Xiao X, Perez R . 6-Hydroxydopamine induces dopaminergic cell degeneration via a caspase-9-mediated apoptotic pathway that is attenuated by caspase-9dn expression. J Neurosci Res. 2004; 77(5):747-61. DOI: 10.1002/jnr.20198. View