PDEs are a family of enzymes that catalyze the hydrolysis of intracellular cyclic nucleotides. They are implicated in a number of disorders and dysfunctions and PDE inhibitors have already proven to be effective therapies for erectile dysfunction, COPD, and psoriatic arthritis. This family of enzymes also plays a role in diseases and disorders of the CNS such as depression, anxiety, schizophrenia, and Alzheimer’s Disease. Unfortunately no effective PDE inhibitors have been developed for the treatment of these diseases. The proposed book will be a comprehensive overview of the current state of basic and translational research on PDE inhibitors written by internationally recognized experts. Authors will also discuss potential PDE subtypes and splice variants in the hopes that this will spur more creative approaches to PDE targeting drugs.
Part I. PDEs and Signaling, Circuitry, and Implications of CNS Functions and Disorders.- 1. Phosphodiesterase Diversity and Signal Processing within cAMP Signaling Networks.- 2. Current Understanding of PDE10A in the Modulation of Basal Ganglia Circuitry.- 3. Interaction of Cdk5 and cAMP/PKA Signaling in the Mediation of Neuropsychiatric and Neurodegenerative Diseases.- 4. The PDE4 cAMP-specific Phosphodiesterases: Targets for Drugs with Antidepressant and Memory-enhancing Action.- 5. Phosphodiesterase-4B as a Therapeutic Target for Cognitive Impairment and Obesity-related Metabolic Diseases.- Part II. PDEs in Cognition of Aging and Alzheimer’s Disease.- 6. From age-related Cognitive Decline to Alzheimer’s Disease: A Translational Overview of the Potential role for Phosphodiesterases.- 7. The Past, Present, and Future of Phosphodiesterase-4 Modulation for age-induced Memory Loss.- 8. A Role for Phosphodiesterase 11A (PDE11A) in the Formation of Social Memories and the Stabilization of Mood.- 9. Role of PDE9 in Cognition.- Part III. PDEs in Parkinson’s and Huntington’s Diseases.- 10. Regulation of Striatal Neuron Activity by Cyclic Nucleotide Signaling and Phosphodiesterase Inhibition: Implications for the Treatment of Parkinson’s Disease.- 11. Role of Phosphodiesterases in Huntington’s Disease.- Part IV. PDEs and Psychiatric Disorders.- 12. The role of Phosphodiesterase-2 in Psychiatric and Neurodegenerative Disorders.- 13. Phosphodiesterase 1: A Unique Drug Target for Degenerative Diseases and Cognitive Dysfunction.- 14. PDE Inhibitors for the Treatment of Schizophrenia.- Part V. PDEs and Others.- 15. Targeting Phosphodiesterases in Pharmacotherapy for Substance Dependence.- 16. Genetic Understanding of Stroke Treatment: Potential role for Phosphodiesterase Inhibitors.- 17. A unique sub-pocket for Improvement of Selectivity of Phosphodiesterase Inhibitors in CNS.
Dr. Han-Ting Zhang received his M.D. from Southern Medical University (formerly the First Military Medical University) in Guangzhou and M.S. and Ph.D. of Pharmacology from Beijing Institute of Pharmacology & Toxicology, the Military Academy of Medical Sciences, China in 1995. He worked as a postdoctoral fellow at Louisiana State University Health Sciences Center in 1998 and then at University of Tennessee Health Science Center in 2000. In 2005 Dr. Zhang joined the Departments of Behavioral Medicine & Psychiatry and Physiology & Pharmacology as a faculty at West Virginia University School of Medicine, Morgantown, WV, USA. He has been a tenured Associate Professor there since 2012. Dr. Zhang is also a “Taishan Scholars” Overseas Distinguished Expert and Professor of Pharmacology at Taishan Medical University (adjunct), China.
Dr. Zhang’s major research interests focus on intracellular signaling in the mediation of neurodegenerative and psychiatric disorders. More specifically, he is interested in exploring the roles of phosphodiesterase (PDE)-mediated cyclic nucleotide (cAMP, cGMP) signaling in depression, anxiety, alcohol dependence, drug abuse, and cognition deficits associated with neurodegenerative disorders such as Alzheimer disease. Development of novel drugs for treating these disorders is also one of his research foci.
Dr. Zhang has published nearly 80 research papers and review articles and 18 book chapters, most of which focusing on PDEs, in particular the PDE4 enzyme family. He has been awarded the NARSAD Young Investigator Award twice (2006 and 2008). Dr. Zhang has been served as the Guest Chief Editor of Current Pharmaceutical Design and currently serves as the Deputy Chief Editor/Associate Editor for Metabolic Brain Disease, Frontiers in Pharmacology, Frontiers in Aging Neuroscience, Translational Neuroscience Review, Austin Psychiatry, and Editorial Board member for Scientific Reports and several other international journals.
Dr. James M. O’Donnell received his B.S. in Psychology from Carnegie Mellon University and Ph.D. in Pharmacological and Physiological Sciences from the University of Chicago; he completed postdoctoral training in Neuropsychopharmacology at the University of Pennsylvania. He was appointed the eleventh Dean of the University at Buffalo School of Pharmacy and Pharmaceutical Sciences in 2013, where he also holds academic appointments as Professor of Pharmaceutical Sciences and Professor of Pharmacology and Toxicology (adjunct). Previously, he held research or faculty positions at Los Alamos National Laboratory, Louisiana State University, University of Tennessee, and West Virginia University, where he served as Associate Dean for Research in the School of Medicine and Assistant Vice President for Health Sciences Research.
Dr. O’Donnell’s research has focused on the relationship between the neurochemical and behavioral effects of drugs, primarily those used to treat neuropsychiatric illnesses. This work has been supported by the NIH, primarily the National Institute of Mental Health, and has involved collaborations with scientists at other universities and biotech and pharmaceutical companies. He has been active in teaching professional and graduate students in the areas of pharmacology and neuroscience and served as Director of an NIGMS-supported, T32 predoctoral training grant at the interface of behavioral and biomedical sciences.
He has served on NIH review panels in the neuroscience and drug discovery areas, including as founding Chair of the Pathophysiological Basis of Mental Disorders and Addictions study section, and is Associate Editor for the Journal of Pharmacology and Experimental Therapeutics. He is a member of a number of scientific and professional societies, was elected Fellow of the American College of Neuropsychopharmacology, and co-chaired the Gordon Research Conference on Cyclic Nucleotide Phosphodiesterases.
PDEs are a family of enzymes that catalyze the hydrolysis of intracellular cyclic neucleotides. They are implicated in a number of disorders and dysfunctions and PDE inhibitors have already proven to be effective therapies for erectile dysfunction, COPD, and psoriatic arthiritis. This family of enzymes also plays a role in diseases and disorders of the CNS such as depression, anxiety, schizophrenia, and Alzheimer’s Disease. Unfortunately no effective PDE inhibitors have been developed for the treatment of these diseases. The proposed book will be a comprehensive overview of the current state of basic and translational research on PDE inhibitors written by internationally recognized experts. Authors will also discuss potential PDE subtypes and splice variants in the hopes that this will spur more creative approaches to PDE targeting drugs. 30 internationally recognized experts on PDEs provide a comprehensive overview of their roles in the CNS
First book to cover all PDEs and their related neurological diseases and disorders
Authors suggest creative ways to target PDEs for better therapeutic results