Abstract
Cyclic AMP and cyclic GMP are essential second messengers that regulate multiple signaling pathways in virtually all cell types. Their accumulation in cells is finely regulated by cyclic nucleotide phosphodiesterases (PDEs), the only enzymes that can degrade these signaling molecules and thus provide exquisite control over intracellular signaling processes. One PDE family, PDE10A, is highly enriched in the brain and its unique expression profile in specific brain regions of interest, in particular to antipsychotic treatment, has made it an attractive therapeutic target for the treatment of schizophrenia. However, after a Phase II trial failure of a selective PDE10A inhibitor for the treatment of schizophrenia, it has encouraged the field to reexamine the role of this enzyme in the brain, and the possible CNS disorders in which PDE10A inhibition could be therapeutic. We will review the localization of PDE10A, both within the brain and the neuron and discuss how its role in regulating cAMP and cGMP accumulation modulates intracellular signaling pathways. Since this cellular signaling has best been documented in the striatum, we will focus our discussion of PDE10A in the context of disorders that affect the basal ganglia, including psychiatric disorders such as bipolar disorder and autism spectrum disorders and the movement disorders, including Parkinson’s disease and Huntington’s disease.
Keywords: Cyclic AMP, cyclic GMP, phosphodiesterase 10A (PDE10A), genetics.
Current Pharmaceutical Design
Title:Emerging Biology of PDE10A
Volume: 21 Issue: 3
Author(s): Lindsay S. Wilson and Nicholas J. Brandon
Affiliation:
Keywords: Cyclic AMP, cyclic GMP, phosphodiesterase 10A (PDE10A), genetics.
Abstract: Cyclic AMP and cyclic GMP are essential second messengers that regulate multiple signaling pathways in virtually all cell types. Their accumulation in cells is finely regulated by cyclic nucleotide phosphodiesterases (PDEs), the only enzymes that can degrade these signaling molecules and thus provide exquisite control over intracellular signaling processes. One PDE family, PDE10A, is highly enriched in the brain and its unique expression profile in specific brain regions of interest, in particular to antipsychotic treatment, has made it an attractive therapeutic target for the treatment of schizophrenia. However, after a Phase II trial failure of a selective PDE10A inhibitor for the treatment of schizophrenia, it has encouraged the field to reexamine the role of this enzyme in the brain, and the possible CNS disorders in which PDE10A inhibition could be therapeutic. We will review the localization of PDE10A, both within the brain and the neuron and discuss how its role in regulating cAMP and cGMP accumulation modulates intracellular signaling pathways. Since this cellular signaling has best been documented in the striatum, we will focus our discussion of PDE10A in the context of disorders that affect the basal ganglia, including psychiatric disorders such as bipolar disorder and autism spectrum disorders and the movement disorders, including Parkinson’s disease and Huntington’s disease.
Export Options
About this article
Cite this article as:
S. Wilson Lindsay and J. Brandon Nicholas, Emerging Biology of PDE10A, Current Pharmaceutical Design 2015; 21 (3) . https://dx.doi.org/10.2174/1381612820666140826114744
DOI https://dx.doi.org/10.2174/1381612820666140826114744 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Adult Treatment Informed By Transference-Countertransference Phenomena Typical For Adolescents
Adolescent Psychiatry Systemic Redox Biomarkers in Neurodegenerative Diseases
Current Drug Metabolism Role of Dopamine Signaling in Drug Addiction
Current Topics in Medicinal Chemistry Role of NF-κB in the Regulation of Cytochrome P450 Enzymes
Current Drug Metabolism The Role of Malnutrition in Older Persons with Mobility Limitations
Current Pharmaceutical Design Therapeutic Targeting of TRPV1 by Resiniferatoxin, from Preclinical Studies to Clinical Trials
Current Topics in Medicinal Chemistry Novel Therapeutic Effects of the Anti-Convulsant, Zonisamide, on Parkinsons Disease
Current Pharmaceutical Design Therapies in Development for Non-Infectious Uveitis
Current Molecular Medicine Disorders of Consciousness and Pharmaceuticals that Act on Oxygen Based Amino Acid and Monoamine Neurotransmitter Pathways of the Brain
Current Pharmaceutical Design The Mitochondrial Dynamics of Alzheimers Disease and Parkinsons Disease Offer Important Opportunities for Therapeutic Intervention
Current Pharmaceutical Design Subject Index Volume 2
Current Pediatric Reviews Thymic Nurse Cells Participate in Heterotypic Internalization and Repertoire Selection of Immature Thymocytes; Their Removal from the Thymus of Autoimmune Animals May be Important to Disease Etiology
Current Molecular Medicine Transglutaminase-Catalyzed Crosslinking in Neurological Disease: From Experimental Evidence to Therapeutic Inhibition
CNS & Neurological Disorders - Drug Targets Bacopa monnieri Supplements Offset Paraquat-Induced Behavioral Phenotype and Brain Oxidative Pathways in Mice
Central Nervous System Agents in Medicinal Chemistry RhoGEFs in Cell Motility: Novel Links Between Rgnef and Focal Adhesion Kinase
Current Molecular Medicine Adolescent Risk Pathways Toward Schizophrenia: Sustained Attention and the Brain
Current Topics in Medicinal Chemistry Transforming Growth Factor-Beta and the Kidney: What We Know and What We Can Do?
Current Enzyme Inhibition A Review of 2,3-Benzodiazepine-related Compounds: Diazepines and 1,2,5- Triazepines Fused with Five-membered Nitrogen Heterocycles
Current Organic Synthesis Exercise and Cognitive-Behavioural Treatment in Fibromyalgia Syndrome
Current Pharmaceutical Design 5-HT3 Receptors: A Potential Therapeutic Target for Epilepsy
Current Neuropharmacology