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PARP as a Therapeutic Target




ISBN 9780849300738
Published March 6, 2002 by CRC Press
360 Pages 65 B/W Illustrations

 
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Book Description

Recent research in cell death mechanisms has rekindled interest in PARP's (Poly (ADP-Ribose) Polymerase) intriguing role in necrosis and apoptosis. While the details of how PARP1 functions are still being elucidated, it has tremendous potential as a promising drug target. PARP inhibitors' dual actions of preventing cell death and abating inflammation have demonstrated remarkable acute effects in animal models of various diseases.

PARP as a Therapeutic Target covers the clinical aspects of this up-and-coming drug that counteracts the damage done by free radicals. Leading international experts currently working on ways to apply it share their views of recent developments and future directions of PARP research. They discuss its therapeutic potential in various disease conditions, such as ischemia, diabetes, cancer, arthritis, inflammatory bowel disease, and septic shock.

The intensified PARP drug development effort has raised expectations for possible clinical trials in the near future to establish the tolerance of PARP inhibitors in healthy humans, its efficacy in treating patients with different diseases, and the long term effect of PARP inhibition. PARP as a Therapeutic Target provides a comprehensive understanding of how PARP works to aid in the better design of its inhibitors for therapeutic purposes.

Table of Contents

Foreword
Nathan A. Berger

Preface
Jie Zhang

Nervous System Functions of Poly(ADP-Ribose) Polymerase-1
Krishna Juluri, Hyo Chol Ha, and Solomon H. Snyder

Role of Poly(ADP-ribose) Polymerase-1 in Neurologic Disorders
Marc F. Poitras, Valina L. Dawson, and Ted M. Dawson

Involvement of PARP-1 and Poly(ADP-Ribosyl)ation in the Maintenance of Genomic Stability
Cynthia M. Simbulan-Rosenthal, Dean S. Rosenthal, Bassem H. Haddad, Danith Ly, Jie Zhang, and Mark E. Smulson

Functional Testing of Human PARP in Proliferation, Endotoxic Shock, and Radiosensitivity: A Genetic Rescue Study
Zdenko Herceg, Virginie Petrilli, Anton Wutz, Bernhard Auer, Marie-Pierre Cros, and Zhao-Qi Wang

PARP Inhibitors as Neuroprotective Agents for Brain Injury
Joel H. Greenberg, Michelle C. LaPlaca, and Tracy K. McIntosh

PARP Inhibitors and Cardioprotection
Christoph Thiemermann, Nicole Wayman, Michelle C. McDonald, and Prabal K. Chatterjee

Neuroprotection of the Retina with 3-Aminobenzamide, a PARP Inhibitor
Tim T. Lam

Poly(ADP-ribose) Polymerase Inhibitors and Acute Renal Failure
Prabal Kumar Chatterjee and Christoph Thiemermann

Role of Poly(ADP-ribose) Polymerase Activation in the Pathogenesis of Shock and Inflammation
Csaba Szabo

Clinical Development of the Nicotinamides and Benzamides Involving PARP as a Molecular Target
Ronald W. Pero, Anders Olsson, Hann Lindgren, and Tomas Leanderson

Chemoprotective Effect of a Novel PARP Inhibitor
Gyorgy Rabloczky, Laszlo Jaszlits, Gyorgy Bardos, Balazs Sumegi, Kalman Tory, Ildiko Racz, Beatrix Farkas, Attila Sandor, Zoltan Berente, Erzsebet Osz, Judit Szilvassy, Istvan Sziklai, Sandor Bernath, and Peter Literati Nagy

Beneficial Effect of GPI 6150 Treatment in Multiple Animal Models of Diseases
Jie Zhang

Protecting Effect of PARP Inhibition on Ultraviolet Light-Induced Skin Damage
Beatrix Farkas, Balazs Sumegi, Gyorgy Rabloczky, Bela Csete, Balazs Hodosi, Marta Magyarlaki, Sandor Bernath, and Peter Literati Nagy

Role of Poly(ADP-Ribose) Polymerase Activation in the Pathogenesis of Diabetes Mellitus and Diabetic Vascular Dysfunction
Jon Mabley, Laszlo Virag, and Csaba Szabo

Therapeutic Targeting of the PARPs: Future Challenges, Future Opportunities
Myron K. Jacobson and Elaine L. Jacobson

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