Therapeutic Role of Synaptic Vesicle Glycoprotein 2A (SV2A) in Modulating Epileptogenesis

CNS & Neurological Disorders Drug Targets
Yukihiro Ohno, Kentaro Tokudome

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 dis...Continue Reading

References

Nov 15, 2019·CNS & Neurological Disorders Drug Targets·Seyed Khosrow TayebatiFrancesco Amenta
Oct 18, 2019·The Journal of Pharmacology and Experimental Therapeutics·Martyn WoodMichel Gillard
Jan 29, 2020·Current Neuropharmacology·Nian YuQing Di

Related Concepts

Bone Diseases, Developmental
Study
Kindling, Neurologic
Pathogenic Aspects
Research
Sv2a
Pathogenesis
Neurotransmitter Secretion
Regulation of Biological Process
SV2A protein, human

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