Phosphodiesterases : CNS functions and diseases

Description

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. Front Matter ....Pages i-xix Front Matter ....Pages 1-1 Phosphodiesterase Diversity and Signal Processing Within cAMP Signaling Networks (Susana R. Neves-Zaph)....Pages 3-14 Current Understanding of PDE10A in the Modulation of Basal Ganglia Circuitry (Jan-Philip Schülke, Nicholas J. Brandon)....Pages 15-43 Interaction of Cdk5 and cAMP/PKA Signaling in the Mediation of Neuropsychiatric and Neurodegenerative Diseases (Yafang Hu, Suyue Pan, Han-Ting Zhang)....Pages 45-61 The PDE4 cAMP-Specific Phosphodiesterases: Targets for Drugs with Antidepressant and Memory-Enhancing Action (Graeme B. Bolger)....Pages 63-102 Phosphodiesterase-4B as a Therapeutic Target for Cognitive Impairment and Obesity-Related Metabolic Diseases (Steven J. Clapcote)....Pages 103-131 Front Matter ....Pages 133-133 From Age-Related Cognitive Decline to Alzheimer’s Disease: A Translational Overview of the Potential Role for Phosphodiesterases (Pim R. A. Heckman, Arjan Blokland, Jos Prickaerts)....Pages 135-168 The Past, Present, and Future of Phosphodiesterase-4 Modulation for Age-Induced Memory Loss (Rolf T. Hansen III, Han-Ting Zhang)....Pages 169-199 A Role for Phosphodiesterase 11A (PDE11A) in the Formation of Social Memories and the Stabilization of Mood (Michy P. Kelly)....Pages 201-230 Role of PDE9 in Cognition (C. Dorner-Ciossek, K. S. Kroker, H. Rosenbrock)....Pages 231-254 Front Matter ....Pages 255-255 Regulation of Striatal Neuron Activity by Cyclic Nucleotide Signaling and Phosphodiesterase Inhibition: Implications for the Treatment of Parkinson’s Disease (Fernando E. Padovan-Neto, Anthony R. West)....Pages 257-283 Role of Phosphodiesterases in Huntington’s Disease (Francesca R. Fusco, Emanuela Paldino)....Pages 285-304 Front Matter ....Pages 305-305 The Role of Phosphodiesterase-2 in Psychiatric and Neurodegenerative Disorders (Chong Zhang, Lindsay M. Lueptow, Han-Ting Zhang, James M. O’Donnell, Ying Xu)....Pages 307-347 Phosphodiesterase 1: A Unique Drug Target for Degenerative Diseases and Cognitive Dysfunction (Lawrence P. Wennogle, Helen Hoxie, Youyi Peng, Joseph P. Hendrick)....Pages 349-384 PDE Inhibitors for the Treatment of Schizophrenia (Gretchen L. Snyder, Kimberly E. Vanover)....Pages 385-409 Front Matter ....Pages 411-411 Targeting Phosphodiesterases in Pharmacotherapy for Substance Dependence (Rui-Ting Wen, Jian-Hui Liang, Han-Ting Zhang)....Pages 413-444 Genetic Understanding of Stroke Treatment: Potential Role for Phosphodiesterase Inhibitors (Anjana Munshi, Satrupa Das)....Pages 445-461 A Unique Sub-Pocket for Improvement of Selectivity of Phosphodiesterase Inhibitors in CNS (Yousheng Wang, Hengming Ke)....Pages 463-471