Synaptic Vesicle Protein 2A as a Novel Pharmacological Target with Broad Potential for New Antiepileptic Drugs

Abstract

In recent years, synaptic vesicle protein 2A (SV2A) has become an attractive protein to study due to its important role in epilepsy. This protein is expressed ubiquitously throughout the brain in all nerve terminals independently of their neurotransmitter. It plays an important role in ensuring correct neurotransmission by priming vesicles for fusion. SV2A is the molecular target of the anticonvulsant drug levetiracetam (LEV), whose effects might be modulated by neuronal activity, by the pathophysiology of the nervous tissue and by SV2A expression. All of these qualities offer the advantage that some anticonvulsant drugs, by interacting with SV2A, could act on both excitatory and inhibitory synapses and simultaneously have effects restricted to epileptic tissue, resulting in the selective modulation of neuronal excitability. This chapter describes and discusses some of the basic aspects of the role of SV2A in epilepsy, addressing three main issues: SV2A function in neurotransmission, the correlation of the expression and/or distribution of the protein with treatment response and neuronal damage, and the reasons that SV2A is a good molecular target for the discovery of new antiepileptic drugs (AEDs).