Apoptosis in Health and Disease: Clinical and Therapeutic Aspects

by Edited by Martin Holcik , Eric C. LaCasse , Alex E. MacKenzie , Robert G. Korneluk

• ISBN13: 9780521529563
• ISBN10: 0521529565
• Format: Hardcover
• Copyright: 2005-03-28
• Publisher: Cambridge University Press

Summary

The process of programmed cell death or apoptosis has, in the past decade, been shown to be centrally involved in the pathogenesis of the significant majority of human illnesses and injury states. The cellular attrition observed in most degenerative conditions is apoptotic in nature; conversely a failure of apoptosis has been proposed to underlie many forms of cancer. The central role of apoptosis in human disease clearly brings with it clinical promise; for example, the strong possibility exists that attenuation of apoptotic death will significantly modulate the severity of degenerative disorders. Similarly, conditions, such as cancer, autoimmune disease, psoriasis and endometriosis, in which aberrant cellular proliferation is observed, may benefit from enhanced rates of apoptosis. This book surveys the underlying molecular mechanisms of apoptosis, investigates its role in degenerative and other diseases, and evaluates potential therapies that will permit appropriate activation or inhibition of apoptosis in disease and injury states.

Table of Contents

List of contributors	vii
Preface	ix
1 Apoptosis in health, disease, and therapy: overview and methodology	1	(48)
Eric C. LaCasse, Martin Holcik, Robert G. Korneluk, and Alex E. MacKenzie
1.1 Introduction: life cannot exist without cellular death	1	(9)
1.2 Apoptosis: roles in health	10	(1)
1.3 Apoptosis: roles in disease	11	(6)
1.4 Therapeutic strategies targeting apoptosis	17	(7)
1.5 Methods in apoptosis research	24	(4)
1.6 Conclusion	28	(21)
2 Developmental apoptosis in health and disease	49	(26)
Hyung Don Ryoo and Hermann Steller
2.1 Introduction	49	(1)
2.2 Apoptosis in C. elegans	50	(4)
2.3 Apoptosis in Drosophila	54	(7)
2.4 Apoptosis during mammalian development	61	(14)
3 Apoptosis and cancer	75	(21)
Erinn L. Soucie, Gerard Evan, and Linda Z. Penn
3.1 Introduction	75	(1)
3.2 Defining cancer in apoptotic terms	75	(2)
3.3 Molecular mechanisms of apoptotic deregulation in cancers	77	(5)
3.4 Reactivating the death pathway to combat cancer	82	(6)
3.5 On the horizon	88	(1)
3.6 Conclusions	89	(7)
4 Neuronal cell death in human neurodegenerative diseases and their animal/cell models	96	(60)
Lee J. Martin, Zhiping Liu, Juan Troncoso, and Donald L. Price
4.1 Introduction	96	(1)
4.2 Types of cell death	96	(6)
4.3 Molecular and cellular regulation of apoptosis	102	(13)
4.4 Regulation of developmental PCD in the nervous system	115	(1)
4.5 Cell death in human neurodegenerative diseases	115	(41)
5 Apoptosis in the cardiovascular system: incidence, regulation, and therapeutic options	156	(32)
Martin R. Bennett
5.1 Incidence of apoptosis	156	(6)
5.2 Regulation of apoptosis	162	(8)
5.3 Therapeutic options for apoptosis treatment	170	(4)
5.4 Outstanding questions	174	(1)
5.5 Summary	175	(13)
6 Cytotoxic lymphocytes, apoptosis, and autoimmunity	188	(31)
Pere Santamaria and R. Chris Bleackley
6.1 Introduction	188	(1)
6.2 Cell-mediated cytotoxicity: kissing the offender	189	(3)
6.3 TNF/TNFR family members and CTL killing without target cell engagement: looks can kill	192	(2)
6.4 Apoptosis and autoimmunity	194	(10)
6.5 Concluding remarks	204	(15)
7 Pro- and anti-apoptotic strategies of viruses	219	(27)
Helmut Fickenscher, Bernhard Fleckenstein, and Armin Ensser
7.1 Introduction	219	(1)
7.2 Major anti-apoptotic pathways targeted by viruses	220	(8)
7.3 Specific viral strategies to induce or block apoptosis	228	(6)
7.4 Conclusions	234	(12)
Index	246