Cyclic-Nucleotide Phosphodiesterases in the Central Nervous System From Biology to Drug Discovery

by Brandon, Nicholas J.; West, Anthony R.

• ISBN13: 9780470566688
• ISBN10: 047056668X
• Edition: 1st
• Format: Hardcover
• Copyright: 2014-04-28
• Publisher: Wiley

Summary

This book reviews advances in understanding phosphodiesterases within the central nervous system and their therapeutic applications. A range of expert authors from both academia and industry describe these, then focus on the areas of greatest scientific and medical interest to provide more detailed coverage. Therapeutic and drug discovery applications are covered for diseases including Alzheimer's, Parkinson's, schizophrenia, erectile dysfunction, and spinal cord injuries. There is also a chapter on drug discovery tools such as in vitro assays and X-ray structures for medicinal chemistry studies.

Author Biography

NICHOLAS BRANDON works at AstraZeneca within the Neuroscience Innovative Medicines Group. He has spent his career in drug discovery with a strong interest in developing phosphodiesterase inhibitors for neuropsychiatric disorders and understanding the basic mechanisms of phosphodiesterase function.

ANTHONY WEST is an Associate Professor in the Department of Neuroscience at Rosalind Franklin University. He has studied PDE function in the basal ganglia for over fifteen years, focusing on neurochemical and electrophysiological changes induced by PDE inhibitors in the healthy brain and in animal models of Parkinson’s disease and Huntington’s disease.

Table of Contents

1 Phosphodiesterases and Cyclic Nucleotide Signaling in the CNS
Marco Conti and Wito Richter

2 Putting together the pieces of phosphodiesterase distribution patterns in the brain: A jigsaw puzzle of cyclic nucleotide regulation
Michy P. Kelly

3 Compartmentalization and regulation of cyclic nucleotide signalling in the CNS
Manuela Zaccolo and Alessandra Stangherlin

4 Pharmacological manipulation of cyclic nucleotide phosphodiesterase signaling for the treatment of neurological and psychiatric disorders in the brain
Frank S. Menniti, Niels Plath, Christopher J. Schmidt, and Niels Svenstrup

5 Recent results in phosphodiesterase inhibitor development and CNS applications
David P. Rotella

6 Crystal structures of phosphodiesterases and implication on discovery of inhibitors
Hengming Ke, Huanchen Wang, Mengchun Ye, and Yingchun Huang

7 Inhibition of cyclic nucleotide phosphodiesterases to regulate memory
Han-Ting Zhang, Ying Xu, James O’Donnell

8 Emerging role for PDE4 in neuropsychiatric disorders: Translating advances from genetic studies into relevant therapeutic strategies
Sandra P. Zoubovsky, Nicholas J. Brandon P, and Akira Sawa

9 Beyond erectile dysfunction: Understanding PDE5 activity in the central nervous system
Eva P. P. Bollen, Kris Rutten, Olga A. H. Reneerkens, Harry M.W Steinbusch, and Jos Prickaerts

10 Molecular and cellular understanding of PDE10A: A dual-substrate phosphodiesterase with therapeutic potential to modulate basal ganglia function
Erik I. Charych and Nicholas J. Brandon

11 Role of cyclic nucleotide signaling and phosphodiesterase activation in the modulation of electrophysiological activity of central neurons
Sarah Threlfell and Anthony R. West

12 The role of phosphodiesterases in dopamine systems governing motivated behavior
Gretchen L. Snyder, Akinori Nishi, and Joseph P. Hendrick

13 Inhibition of phosphodiesterases as a strategy for treatment of spinal cord injury
Elena Nikulina and Marie T. Filbin