SV2A

SV2A, or synaptic vesicle glycoprotein 2A, is a member of the SV2 family of integral membrane proteins located on synaptic vesicles in neurons. It is encoded by the SV2A gene in humans. SV2A is widely expressed in the central nervous system, with particularly high levels in the cortex and hippocampus, and it is also present in some neuroendocrine cells.

Structurally, SV2A proteins are predicted to have 12 transmembrane helices with cytoplasmic N- and C- termini and several glycosylated luminal loops. They are embedded in the membrane of small synaptic vesicles and participate in vesicle cycling and exocytosis.

Functionally, SV2A is thought to regulate Ca2+-dependent neurotransmitter release by influencing vesicle priming and the availability of release-ready vesicles. The precise mechanism is not fully understood, but SV2A interacts with components of the SNARE complex and may coordinate neurotransmitter release. Loss of SV2A in animal models leads to impaired synaptic transmission and severe seizures, with perinatal lethality in mice.

Clinically, SV2A is best known as the molecular target of the antiepileptic drug levetiracetam and related compounds such as brivaracetam. Binding to SV2A alters synaptic function and reduces seizure activity. SV2A expression and function are also investigated as biomarkers of synaptic density; several PET radioligands (for example, 11C-UCB-J) are used to image synaptic density in the brain.

Research continues into the role of SV2A in neurological disorders beyond epilepsy, including potential implications for neurodegenerative and neurodevelopmental diseases, as well as the development of SV2A-targeted therapies and imaging tools.