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Chapter category: Apoptosis

Caspases as Targets for Drug Development

This chapter appears in the following book:

Caspases: Their Role in Cell Death and Cell Survival

Edited by: Marek Los and Henning Walczak
ISBN: 0-306-47441-7
» Get more information about this book at landesbioscience.com «

Chapter authors:
Manuela Michalke, Anna Stepczynska, Malgorzata Burek, Truc Nguyen Bui, Karin Loser, Krzysztof Krzemieniecki and Marek Los


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Controlled cell proliferation, differentiation, activation and cell removal are the key events during the development and existence of multicellular organisms. Proliferating mammalian cells undertake a repeated sequence of DNA synthesis, mitosis, and cell division, a series of complicated processes that when going astray, may become deleterious not only to the particular cell, but also to the whole organism. Regulation and proper control of the cell cycle and of the programmed cell death (PCD, apoptosis) is therefore essential for mammalian development and tissue homeostasis. The molecular networks that regulate these processes are critical targets for drug development, gene therapy, and metabolic engineering. In this chapter we will focus on apoptotic pathways converging on caspase family proteases, summarizing "under development" pharmacological attempts towards genes, proteins, and intermolecular interactions presently known to control apoptosis. We also propose new potential molecular targets that may prove to be effective in controlling cell death in vivo.

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Additional chapters from this book:

Other Methods of Caspase Activity Monitoring

Hubert Hug, Christof Burek and Marek Los

Caspases (Cysteine-Aspart-ases) are important effector molecules involved in apoptosis, though some of them can also participate in other physiological processes such as a...

In Situ Activation of Caspases Revealed by Affinity Labeling Their Enzymatic Sites

Jerzy Grabarek and Zbigniew Darzynkiewicz

Activation of caspases is the key event of apoptosis as its initiates irreversible steps of the cell demise.1-9 Several methods, therefore, have been developed to monitor this event...

Caspases as Targets for Drug Development

Manuela Michalke, Anna Stepczynska, Malgorzata Burek, Truc Nguyen Bui, Karin Loser, Krzysztof Krzemieniecki and Marek Los

Controlled cell proliferation, differentiation, activation and cell removal are the key events during the development and existence of multicellular organisms. Proliferating mammalian cells un...

Caspase-Independent Cell Death Mechanisms

Donat Kögel and Jochen H. M. Prehn

Almost 30 years ago, Kerr and co-workers proposed the existence of an intrinsic cell death program and introduced the term apoptosis for the execution of this program.1 Apoptosis is...

Caspase Activation in Cancer Therapy

Simone Fulda and Klaus-Michael Debatin

Different anticancer therapies including cytotoxic drugs, g-irradiation, suicide gene therapy or immunotherapy, appear to induce tumor cell death by activating key e...

Learning from Deficiency: Gene Targeting of Caspases

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For all multicellular organisms, cell number control is essential for proper organ formation during development, and for cellular homeostatsis in adults.1 Such a critical task requi...

Caspases, Bcl-2 Family Proteins and Other Components of the Death Machinery: Their Role in the Regulation of the Immune Response

Marc Pellegrini and Andreas Strasser

The prime directive of the immune system is to defend the host. The threats can be external in the form of microbial pathogens or internal in the form of rebellious autoreactive or malignant c...

The Role of Caspases in Modulation of Cytokines and other Molecules in Apoptosis and Inflammation

Harald Loppnow, Krzysztof Guzik and Juliusz Pryjma

Caspases are a large family of evolutionary conserved proteases. The first caspase, has been identified as the enzyme necessary for functional maturation of IL-1b.

Virus-Encoded Caspase Inhibitors

Grant McFadden and Richard W. Moyer

There have been many excellent reviews on caspase structure and function16 and key features will only briefly be discussed here to set the framework for our discussion of virus enco...

Modulation of Caspase Activity by Cellular Inhibitors

Klaus W. Wagner, Badry D. Bursulaya and Quinn L. Deveraux

Caspases are key effectors of the apoptosis process, therefore it is not surprising that mammals, as well as other species, evolved molecules that regulate caspases by directly binding and inh...

Mitochondrial/Apoptosome Dependent Activation of Caspases

Kelvin Cain

Many key biological processes, including caspase activation during apoptotic cell death are executed by large multi-protein complexes. Apoptosis can be initiated via death receptors or by pert...

Caspase Activation at the TNF-R Family Members Death Inducing Signaling Complexes (DISCs)

Martin R. Sprick and Henning Walczak

During the life span of a multicellular organism most cells die at a certain point. The decision to die serves the common purpose of all cells in such organisms which is self propagation. Mult...

Caspase Cascades in Apoptosis

Colin Adrain, Emma M. Creagh and Seamus J. Martin

Apoptosis can be thought of as a controlled demolition process that ensures the safe dismantling of cellular structures and removal of the resulting debris such that collateral damage to surro...

The Caspase Family

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Caspases, a family of cysteinyl aspartate-specific proteases, are central mediators of apoptotic and inflammatory pathways. Caspases are synthesized as zymogens with a prodomain of variable length fol...

Apoptosis Dependent and Independent Functions of Caspases

Alicia Algeciras-Schimnich, Bryan C. Barnhart and Marcus E. Peter

The study of cell death in the nematode Caenorhabditis elegans has led to the identification of several proteins which are responsible for orchestrating cell death. For each of these proteins,...


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