Abstract
Over the years, accumulating evidence has indicated that D-serine represents the endogenous ligand for the glycinemodulatory binding site on the NR1 subunit of N-methyl-D-aspartate receptors in various brain areas. Cellular concentrations of D-serine are regulated by synthesis due to the enzyme serine racemase (isomerization reaction) and by degradation due to the same enzyme (elimination reaction) as well as by the FAD-containing flavoenzyme D-amino acid oxidase (DAAO, oxidative deamination reaction). Several findings have linked low levels of D-serine to schizophrenia: D-serine concentrations in serum and cerebrospinal fluid have been reported to be decreased in schizophrenia patients while human DAAO activity and expression are increased; oral administration of Dserine improved positive, negative, and cognitive symptoms of schizophrenia as add-on therapy to typical and atypical antipsychotics. This evidence indicates that increasing NMDA receptor function, perhaps by inhibiting DAAO-induced degradation of D-serine may alleviate symptoms in schizophrenic patients. Furthermore, it has been suggested that co-administration of D-serine with a human DAAO inhibitor may be a more effective means of increasing D-serine levels in the brain. Here, we present an overview of the current knowledge of the structure-function relationships in human DAAO and of the compounds recently developed to inhibit its activity (specifically the ones recently exploited for schizophrenia treatment).
Keywords: Schizophrenia, D-serine, NMDA receptor, inhibitors
Current Pharmaceutical Design
Title:D-Amino Acid Oxidase Inhibitors as a Novel Class of Drugs for Schizophrenia Therapy
Volume: 19 Issue: 14
Author(s): Silvia Sacchi, Elena Rosini, Loredano Pollegioni and Gianluca Molla
Affiliation:
Keywords: Schizophrenia, D-serine, NMDA receptor, inhibitors
Abstract: Over the years, accumulating evidence has indicated that D-serine represents the endogenous ligand for the glycinemodulatory binding site on the NR1 subunit of N-methyl-D-aspartate receptors in various brain areas. Cellular concentrations of D-serine are regulated by synthesis due to the enzyme serine racemase (isomerization reaction) and by degradation due to the same enzyme (elimination reaction) as well as by the FAD-containing flavoenzyme D-amino acid oxidase (DAAO, oxidative deamination reaction). Several findings have linked low levels of D-serine to schizophrenia: D-serine concentrations in serum and cerebrospinal fluid have been reported to be decreased in schizophrenia patients while human DAAO activity and expression are increased; oral administration of Dserine improved positive, negative, and cognitive symptoms of schizophrenia as add-on therapy to typical and atypical antipsychotics. This evidence indicates that increasing NMDA receptor function, perhaps by inhibiting DAAO-induced degradation of D-serine may alleviate symptoms in schizophrenic patients. Furthermore, it has been suggested that co-administration of D-serine with a human DAAO inhibitor may be a more effective means of increasing D-serine levels in the brain. Here, we present an overview of the current knowledge of the structure-function relationships in human DAAO and of the compounds recently developed to inhibit its activity (specifically the ones recently exploited for schizophrenia treatment).
Export Options
About this article
Cite this article as:
Sacchi Silvia, Rosini Elena, Pollegioni Loredano and Molla Gianluca, D-Amino Acid Oxidase Inhibitors as a Novel Class of Drugs for Schizophrenia Therapy, Current Pharmaceutical Design 2013; 19 (14) . https://dx.doi.org/10.2174/1381612811319140002
DOI https://dx.doi.org/10.2174/1381612811319140002 |
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
-
SNP Web Resources and Their Potential Applications in Personalized Medicine
Current Drug Metabolism Hapten Recognition by T Cells: A Functional and Molecular View
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Assessing the Effectiveness of a Telemedicine Initiative in Clinical Management of Children Living with HIV/AIDS in Maharashtra, India
Current HIV Research Management of Glia-Mediated Neuroinflammation and Related Patents
Recent Patents on Inflammation & Allergy Drug Discovery Leptin as a Cardiac Pro-Hypertrophic Factor and its Potential Role in the Development of Heart Failure
Current Pharmaceutical Design Theoretical Formulation Strategies towards Neutralizing Inter-individual Variability Associated with Tacrolimus Immunosuppressant Therapy: A Case Study on Nextgeneration Personalized Medicine
Current Drug Metabolism α7 Nicotinic Acetylcholine Receptors: A Therapeutic Target in the Structure Era
Current Drug Targets The Anabolic Effects of Growth Hormone (GH) and GH Secretagogues on Bone Mass and Density
Medicinal Chemistry Reviews - Online (Discontinued) Benefits of Caloric Restriction on Brain Aging and Related Pathological States: Understanding Mechanisms to Devise Novel Therapies
Current Medicinal Chemistry First Phase Insulin Secretion and Type 2 Diabetes
Current Molecular Medicine Biotherapy for Autoimmune Liver Diseases
Current Pharmaceutical Biotechnology Recent Patents, Formulation and Characterization of Nanoliposomes
Recent Patents on Drug Delivery & Formulation The Role of Microbiota and Intestinal Permeability in the Pathophysiology of Autoimmune and Neuroimmune Processes with an Emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome
Current Pharmaceutical Design Targeting the Atypical Chemokine Receptor ACKR3/CXCR7: Phase 1 - Phage Display Peptide Identification and Characterization
Current Topics in Medicinal Chemistry Neurochemical and Neuropharmacological Aspects of Circadian Disruptions: An Introduction to Asynchronization
Current Neuropharmacology An Overview of Phytotherapeutic Approaches for the Treatment of Benign Prostatic Hyperplasia
Mini-Reviews in Medicinal Chemistry Current Challenges to Overcome in the Management of Type 2 Diabetes Mellitus and Associated Neurological Disorders
CNS & Neurological Disorders - Drug Targets Pharmacological Profile and Pharmacogenomics of Anti-Cancer Drugs Used for Targeted Therapy
Current Cancer Drug Targets Targeting of Antioxidant and Anti-Thrombotic Drugs to Endothelial Cell Adhesion Molecules
Current Pharmaceutical Design Inflammatory and Cell Death Pathways in Brain and Peripheral Blood in Parkinson’s Disease
CNS & Neurological Disorders - Drug Targets