Abstract
The term "Autism Spectrum" is often used to describe disorders that are currently classified as Pervasive Developmental Disorders. These disorders are typically characterized by social deficits, communication difficulties, stereotyped or repetitive behaviors and/or cognitive delays or mental retardation; sometimes they present high comorbidity rates with epilepsy. Although these diagnoses share some common features, individuals with these disorders are thought to be "on the spectrum" because of differences in severity across these domains.
Recent advances in the genetics of autism spectrum disorders (ASDs) are offering new valuable insights into molecular and cellular mechanisms of pathology. Of particular interest are transgenic technologies that allowed the engineering of several mouse models mimicking different kinds of monogenic heritable forms of ASDs. These transgenic models provide excellent opportunities to explore in detail cellular and molecular mechanisms underlying disease pathology and to identify novel targets for therapeutic intervention.
Increasing evidence suggests that the pathophysiological core of the murine model is primarily due to changes in normal synaptic transmission and plasticity.
Here, we will extensively review the synaptic alterations across different animal models of ASDs and recapitulate the pharmacological strategies aimed at rescuing hippocampal plasticity phenotypes. We describe how pharmacological modulation of mGlu5 receptor, through the use of positive or negative allosteric modulators (depending on the specific disorder), may represent a promising therapeutic strategy for ASDs treatment.
Keywords: Synaptic plasticity, long-term potentiation, long-term depression, monogenic autism, mGLURs.
Current Pharmaceutical Design
Title:Synaptic Plasticity as a Therapeutic Target in the Treatment of Autism-related Single-gene Disorders
Volume: 19 Issue: 36
Author(s): Marco Pignatelli, Marco Feligioni, Sonia Piccinin, Gemma Molinaro, Ferdinando Nicoletti and Robert Nisticò
Affiliation:
Keywords: Synaptic plasticity, long-term potentiation, long-term depression, monogenic autism, mGLURs.
Abstract: The term "Autism Spectrum" is often used to describe disorders that are currently classified as Pervasive Developmental Disorders. These disorders are typically characterized by social deficits, communication difficulties, stereotyped or repetitive behaviors and/or cognitive delays or mental retardation; sometimes they present high comorbidity rates with epilepsy. Although these diagnoses share some common features, individuals with these disorders are thought to be "on the spectrum" because of differences in severity across these domains.
Recent advances in the genetics of autism spectrum disorders (ASDs) are offering new valuable insights into molecular and cellular mechanisms of pathology. Of particular interest are transgenic technologies that allowed the engineering of several mouse models mimicking different kinds of monogenic heritable forms of ASDs. These transgenic models provide excellent opportunities to explore in detail cellular and molecular mechanisms underlying disease pathology and to identify novel targets for therapeutic intervention.
Increasing evidence suggests that the pathophysiological core of the murine model is primarily due to changes in normal synaptic transmission and plasticity.
Here, we will extensively review the synaptic alterations across different animal models of ASDs and recapitulate the pharmacological strategies aimed at rescuing hippocampal plasticity phenotypes. We describe how pharmacological modulation of mGlu5 receptor, through the use of positive or negative allosteric modulators (depending on the specific disorder), may represent a promising therapeutic strategy for ASDs treatment.
Export Options
About this article
Cite this article as:
Pignatelli Marco, Feligioni Marco, Piccinin Sonia, Molinaro Gemma, Nicoletti Ferdinando and Nisticò Robert, Synaptic Plasticity as a Therapeutic Target in the Treatment of Autism-related Single-gene Disorders, Current Pharmaceutical Design 2013; 19 (36) . https://dx.doi.org/10.2174/1381612811319360008
DOI https://dx.doi.org/10.2174/1381612811319360008 |
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
-
To Analyze the Amelioration of Phenobarbital Induced Oxidative Stress by Erucin, as Indicated by Biochemical and Histological Alterations
Anti-Cancer Agents in Medicinal Chemistry Persons with Co-Existing Neurological Disorders: Risk Analysis, Considerations and Management in COVID-19 Pandemic
CNS & Neurological Disorders - Drug Targets SiRNA Mediated Gene Silencing: Hurdles, Strategies and Applications
Pharmaceutical Nanotechnology Preface [Hot topic: Carbohydrates (Executive Editor: Istvan Toth)]
Mini-Reviews in Medicinal Chemistry Neurotrophin Receptor Signaling as a Therapeutic Target for Huntington's Disease
CNS & Neurological Disorders - Drug Targets Redox Processes in Neurodegenerative Disease Involving Reactive Oxygen Species
Current Neuropharmacology Signaling Pathways that Regulate Basal ABC Transporter Activity at the Blood- Brain Barrier
Current Pharmaceutical Design Computer-Aided Drug Discovery and Design Targeting Ion Channels
Current Topics in Medicinal Chemistry Lower K<sub>V</sub>7.5 Potassium Channel Subunit Expression in an Animal Model of Paroxysmal Dystonia
CNS & Neurological Disorders - Drug Targets The Non-ABC Drug Transporter RLIP76 (RALBP-1) Plays a Major Role in the Mechanisms of Drug Resistance
Current Drug Metabolism Cardio-Hepatic Metabolic Derangements and Valproic Acid
Current Clinical Pharmacology Personalized Medicine Using Cutting Edge Technologies for Genetic Epilepsies
Current Neuropharmacology Design, Synthesis and Protection Against Pentylenetetrazole-induced Seizure of N-aryl Derivatives of the Phthalimide Pharmacophore
Medicinal Chemistry Semicarbazone Analogs as Anticonvulsant Agents: A Review
Central Nervous System Agents in Medicinal Chemistry TRP Channels: New Potential Therapeutic Approaches in CNS Neuropathies
CNS & Neurological Disorders - Drug Targets Neurochemical Imbalance in Epilepsy from Animal Model to Human
Current Psychopharmacology Securinine Derivatives as Potential Anti-amyloid Therapeutic Approach
CNS & Neurological Disorders - Drug Targets Extraction, GC-MS Evaluation and Anti-epileptic Potential of Seeds Ethanolic Extract of Putranjiva roxburghii Wall
Central Nervous System Agents in Medicinal Chemistry Overview of Childhood Epilepsy and Epileptic Syndromes and Advances in Therapy
Current Pharmaceutical Design Epileptogenicity and Epileptic Activity: Mechanisms in an Invertebrate Model Nervous System
Current Drug Targets