Abstract
Dysfunction of synaptic neurotransmitter release is closely involved in the pathogenesis of various central nervous system diseases. Synaptic vesicle glycoprotein 2A (SV2A) is a membrane protein specifically expressed in synaptic vesicles and it modulates action potential-dependent neurotransmitter release in the brain. Since 1) SV2A-knockout mice exhibit severe convulsive seizures, 2) SV2A expression in the brain is reportedly altered in various epileptic disorders both in animal models (e.g., kindling and genetic models) and humans (e.g., intractable temporal lobe epilepsy and focal cortical dysplasia) and 3) SV2A serves as a specific binding site for the antiepileptic drug, levetiracetam and its analogues, it is considered that SV2A is involved in the pathogenesis and treatment of epilepsy. In addition, a recent clinical study demonstrated that a missense mutation in the SV2A gene caused intractable epilepsy with involuntary movements and developmental retardation, illustrating a causative role of SV2A dysfunction in epilepsy. Although the functional mechanisms of SV2A in regulating epileptogenesis remain unknown, studies using animals carrying the Sv2a missense mutation showed that the dysfunction of SV2A preferentially disrupts action potential-induced γ-aminiobutyric acid (GABA), but not glutamate, released in the limbic regions (i.e., hippocampus and amygdala) and markedly facilitates kindling epileptogenesis. All these evidences indicate that the SV2A-GABAergic system plays a crucial role in modulating epileptogenesis and encourages research on the novel antiepileptic agents which enhance SV2A function.
Keywords: Antiepileptic drugs, epilepsy, epileptogenesis, γ-aminiobutyric acid, glutamate, neurotransmitter release, synaptic vesicle glycoprotein 2A.
CNS & Neurological Disorders - Drug Targets
Title:Therapeutic Role of Synaptic Vesicle Glycoprotein 2A (SV2A) in Modulating Epileptogenesis
Volume: 16 Issue: 4
Author(s): Yukihiro Ohno*Kentaro Tokudome
Affiliation:
- Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094,Japan
Keywords: Antiepileptic drugs, epilepsy, epileptogenesis, γ-aminiobutyric acid, glutamate, neurotransmitter release, synaptic vesicle glycoprotein 2A.
Abstract: Dysfunction of synaptic neurotransmitter release is closely involved in the pathogenesis of various central nervous system diseases. Synaptic vesicle glycoprotein 2A (SV2A) is a membrane protein specifically expressed in synaptic vesicles and it modulates action potential-dependent neurotransmitter release in the brain. Since 1) SV2A-knockout mice exhibit severe convulsive seizures, 2) SV2A expression in the brain is reportedly altered in various epileptic disorders both in animal models (e.g., kindling and genetic models) and humans (e.g., intractable temporal lobe epilepsy and focal cortical dysplasia) and 3) SV2A serves as a specific binding site for the antiepileptic drug, levetiracetam and its analogues, it is considered that SV2A is involved in the pathogenesis and treatment of epilepsy. In addition, a recent clinical study demonstrated that a missense mutation in the SV2A gene caused intractable epilepsy with involuntary movements and developmental retardation, illustrating a causative role of SV2A dysfunction in epilepsy. Although the functional mechanisms of SV2A in regulating epileptogenesis remain unknown, studies using animals carrying the Sv2a missense mutation showed that the dysfunction of SV2A preferentially disrupts action potential-induced γ-aminiobutyric acid (GABA), but not glutamate, released in the limbic regions (i.e., hippocampus and amygdala) and markedly facilitates kindling epileptogenesis. All these evidences indicate that the SV2A-GABAergic system plays a crucial role in modulating epileptogenesis and encourages research on the novel antiepileptic agents which enhance SV2A function.
Export Options
About this article
Cite this article as:
Ohno Yukihiro*, Tokudome Kentaro, Therapeutic Role of Synaptic Vesicle Glycoprotein 2A (SV2A) in Modulating Epileptogenesis, CNS & Neurological Disorders - Drug Targets 2017; 16 (4) . https://dx.doi.org/10.2174/1871527316666170404115027
DOI https://dx.doi.org/10.2174/1871527316666170404115027 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Lifestyle Interventions to Prevent and Treat Cognitive Impairment and Dementia
More than 55 million people live with dementia worldwide. By 2050, the population affected by dementia will exceed 139 million individuals. Mild cognitive impairment (MCI) is a pre-dementia stage, also known as prodromal dementia, affecting older adults. MCI emerges years before the manifestation of dementia but can be avoidable and ...read more
Novel Treatments in Subarachnoid Hemorrhage
The current landscape of therapeutic strategies for subarachnoid hemorrhage (SAH), a significant adverse neurological event commonly resulting from the rupture of intracranial aneurysms, is rapidly evolving. Through an in-depth exploration of the natural history of SAH, historical treatment approaches, and emerging management modalities, the present work aims to provide a ...read more
Pathogenic Proteins in Neurodegenerative Diseases: From Mechanisms to Treatment Modalities
The primary objective of this thematic issue is to elucidate the molecular mechanisms by which pathogenic proteins contribute to neurodegenerative diseases and to highlight current and emerging therapeutic strategies aimed at mitigating their effects. By bringing together cutting-edge research and reviews, this issue aims to: 1.Enhance Understanding: Provide a comprehensive ...read more
Role of glial cells in autism spectrum disorder: Molecular mechanism and therapeutic approaches
Emerging evidence suggests that glial cells may play a pivotal role in neuroanatomical and behavioral changes found in autism spectrum disorder (ASD). Many individuals with ASD experience a neuro-immune system abnormalities throughout life, which implicates a potential role of microglia in the pathogenesis of ASD. Dysfunctional astrocytes and oligodendrocytes were ...read more
![](/images/wayfinder.jpg)
- 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
Related Articles
-
Role of Adenosine Kinase Inhibitor in Adenosine Augmentation Therapy for Epilepsy: A Potential Novel Drug for Epilepsy
Current Drug Targets Early Age of Migraine Onset is Independently Related to Cognitive Decline and Symptoms of Depression Affect Quality of Life
Current Neurovascular Research Role of Nanotechnology for Enzyme Replacement Therapy in Lysosomal Diseases. A Focus on Gaucher’s Disease
Current Medicinal Chemistry Kynurenic Acid and Neuroprotective Activity of the Ketogenic Diet in the Eye
Current Medicinal Chemistry Huntingtons Disease: New Frontiers for Molecular and Cell Therapy
Current Drug Targets An Ion Channel Chip for Diagnosis and Prognosis of Autoimmune Neurological Disorders
Recent Patents on CNS Drug Discovery (Discontinued) Revolutionizing Neurological Disorder Treatment: Integrating Innovations in Pharmaceutical Interventions and Advanced Therapeutic Technologies
Current Pharmaceutical Design The Potential of Trace Amines and Their Receptors for Treating Neurological and Psychiatric Diseases
Reviews on Recent Clinical Trials Trigonelline: A Plant Alkaloid with Therapeutic Potential for Diabetes and Central Nervous System Disease
Current Medicinal Chemistry Targeting the Role of Astrocytes in the Progression of Alzheimers Disease
Current Signal Transduction Therapy Sodium Channel Blockers as Therapeutic Target for Treating Epilepsy: Recent Updates
Current Topics in Medicinal Chemistry The Place of Somatostatin Analogs in the Diagnosis and Treatment of the Neuoroendocrine Glands Tumors
Recent Patents on Anti-Cancer Drug Discovery Synthesis and Anticonvulsant Activity of Some Cinnamylpiperazine Derivatives
Letters in Drug Design & Discovery GABA Transporters and GABA-Transaminase as Drug Targets
Current Drug Targets - CNS & Neurological Disorders Cm38: A New Antimicrobial Peptide Active Against Klebsiella pneumoniae is Homologous to Cn11
Protein & Peptide Letters Topiramate Decelerates Bicarbonate-Driven Acid-Elimination of Human Neocortical Neurons: Strategic Significance for its Antiepileptic, Antimigraine and Neuroprotective Properties
CNS & Neurological Disorders - Drug Targets A Comprehensive Review on the Ethnopharmacology, Phytochemistry, Pharmacology, and Toxicology of the Mandragora Genus; from Folk Medicine to Modern Medicine
Current Pharmaceutical Design Editorial (Thematic Issue: Linkage of Neurodegenerative Disorders with Other Health Issues – Volume I)
CNS & Neurological Disorders - Drug Targets Preface:
Current Topics in Medicinal Chemistry Clinical Utility of Neuronal Cells Directly Converted from Fibroblasts of Patients for Neuropsychiatric Disorders: Studies of Lysosomal Storage Diseases and Channelopathy
Current Molecular Medicine