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.
Innehållsförteckning
PREFACE vii
CONTRIBUTORS ix
1 PHOSPHODIESTERASES AND CYCLIC NUCLEOTIDE SIGNALING IN THE
CNS 1
Marco Conti and Wito Richter
2 PUTTING TOGETHER THE PIECES OF PHOSPHODIESTERASE
DISTRIBUTION PATTERNS IN THE BRAIN: A JIGSAW PUZZLE OF CYCLIC
NUCLEOTIDE REGULATION 47
Michy P. Kelly
3 COMPARTMENTALIZATION AND REGULATION OF CYCLIC NUCLEOTIDE
SIGNALING IN THE CNS 59
Manuela Zaccolo and Alessandra Stangherlin
4 PHARMACOLOGICAL MANIPULATION OF CYCLIC NUCLEOTIDE
PHOSPHODIESTERASE SIGNALING FOR THE TREATMENT OF NEUROLOGICAL AND
PSYCHIATRIC DISORDERS IN THE BRAIN 77
Frank S. Menniti, Niels Plath, Niels Svenstrup, and Christopher
J. Schmidt
5 RECENT RESULTS IN PHOSPHODIESTERASE INHIBITOR DEVELOPMENT
AND CNS APPLICATIONS 115
David P. Rotella
6 CRYSTAL STRUCTURES OF PHOSPHODIESTERASES AND IMPLICATION ON
DISCOVERY OF INHIBITORS 145
Hengming Ke, Huanchen Wang, Mengchun Ye, and Yingchun
Huang
7 INHIBITION OF CYCLIC NUCLEOTIDE PHOSPHODIESTERASES TO
REGULATE MEMORY 171
Han-Ting Zhang, Ying Xu, and James O’Donnell
8 EMERGING ROLE FOR PDE4 IN NEUROPSYCHIATRIC DISORDERS:
TRANSLATING ADVANCES FROM GENETIC STUDIES INTO RELEVANT THERAPEUTIC
STRATEGIES 211
Sandra P. Zoubovsky, Nicholas J. Brandon, and Akira Sawa
9 BEYOND ERECTILE DYSFUNCTION: UNDERSTANDING PDE5 ACTIVITY IN
THE CENTRAL NERVOUS SYSTEM 223
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 247
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
269
Sarah Threlfell and Anthony R. West
12 THE ROLE OF PHOSPHODIESTERASES IN DOPAMINE SYSTEMS
GOVERNING MOTIVATED BEHAVIOR 303
Gretchen L. Snyder, Joseph P. Hendrick, and Akinori
Nishi
13 INHIBITION OF PHOSPHODIESTERASES AS A STRATEGY FOR
TREATMENT OF SPINAL CORD INJURY 353
Elena Nikulina and Marie T. Filbin
INDEX 375
Om författaren
NICHOLAS BRANDON works at Astra Zeneca 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.
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