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Synaptisches Vesikelprotein 2A

Beteiligung an epilepsieassoziierten Prozessen und Interaktionen mit Antikonvulsiva

Synaptic vesicle protein 2A

Involvement in epilepsy-associated processes and interactions with anticonvulsants

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Zusammenfassung

Levetiracetam (LEV) und Brivaracetam (BRV) binden spezifisch an das synaptische Vesikelprotein  2A (SV2A). Das SV2A unterstützt als Teil der präsynaptischen Freisetzungsmaschinerie die Exozytose synaptischer Vesikel und trägt so zur Neurotransmitterfreisetzung bei. Der genaue Mechanismus der SV2A-vermittelten antikonvulsiven Wirkung ist bisher nicht eindeutig geklärt. Eine aktivitätsabhängige Aufnahme von LEV und BRV in synaptische Vesikel mit nachfolgender Verminderung der Neurotransmitterfreisetzung ist jedoch ein plausibler Mechanismus. Im Tiermodell und beim Menschen wurde bei verschiedenen genetischen und erworbenen Epilepsien eine reduzierte SV2A-Expression beobachtet, was je nach Ausmaß eine Therapieresistenz für SV2A-Liganden erklären könnte.

Abstract

Both levetiracetam (LEV) and brivaracetam (BRV) specifically bind to the synaptic vesicle protein 2A (SV2A). Synaptic vesicle protein 2A is part of the presynaptic release machinery, supports exocytosis of synaptic vesicles and thereby contributes to neurotransmitter release. The exact mechanisms of how SV2A binding mediates anticonvulsant effects have not yet been elucidated. However, activity-dependent uptake of LEV and BRV with subsequent reduction of neurotransmitter release seems to be a plausible mechanism. A decrease in SV2A expression was observed in different forms of epilepsy in both humans and animals and this reduction could contribute to pharmacoresistance to SV2A ligands in some individuals.

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Interessenkonflikt

Der korrespondierende Autor weist für sich und seine Koautoren auf folgende Beziehungen hin: R.S. hat ein Referentenhonorar sowie eine gesponserte Kongressteilnahme von EISAI erhalten, erhält ein Honorar als Berater für UCB und hat ein Otfrid-Foerster-Stipendium der Deutschen Gesellschaft für Epileptologie erhalten, mit dem experimentelle Arbeiten zum Thema SV2A und LEV durchgeführt wurden.

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  1. Klinik für Epileptologie, Universitätsklinik Bonn, Sigmund Freud Str. 25, 53127, Bonn, Deutschland

    R. Surges & C.E. Elger

  2. Labor für experimentelle Epileptologie und Kognitionsforschung, Universitätsklinik Bonn, Bonn, Deutschland

    R. Surges

  3. Institut für Neuropathologie, Universitätsklinik Bonn, Bonn, Deutschland

    S. Schoch

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Surges, R., Schoch, S. & Elger, C. Synaptisches Vesikelprotein 2A. Z. Epileptol. 25, 215–221 (2012). https://doi.org/10.1007/s10309-012-0249-3

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