Inhibitory RNA in epilepsy: research tools and therapeutic perspectives.

Epilepsia
Detlev Boison

Abstract

Since its discovery a decade ago, RNA interference (RNAi) has been developed not only into powerful experimental tools but also into promising novel therapeutics. In contrast to conventional antiepileptic drugs (AEDs) that target specific proteins such as ion channels or receptors, RNAi-based therapeutics exploit an endogenous regulatory mechanism of gene expression and thereby are poised to prevent or reverse pathogenetic mechanisms involved in seizure development. Therapeutic RNAi has been widely explored for dominant targets involved in neurodegenerative diseases; however, their use for epilepsy therapy has received less attention. This review discusses potential RNAi-based targets that are of interest for epilepsy therapy, including adenosine kinase (ADK), the key negative regulator of the brain's endogenous anticonvulsant adenosine. Overexpression of ADK, and the resulting adenosine deficiency, are pathologic hallmarks of the sclerotic epileptic brain, and have been implicated in seizure generation. Therefore, RNAi-strategies aimed at reducing ADK (and increasing adenosine) are based on a direct neurochemical rationale that has recently been explored experimentally using ex vivo and in vivo gene therapy approaches. Technic...Continue Reading

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Citations

Feb 1, 2011·Epilepsia·Panos TheofilasDetlev Boison
Mar 19, 2014·Nature Reviews. Neurology·Dimitri M KullmannRobert C Wykes
Sep 6, 2015·Neuropharmacology·Detlev Boison
Mar 27, 2013·The International Journal of Neuroscience·Hao LiuFa-Fa Tian
Apr 18, 2013·Pharmacological Reviews·Detlev Boison
Dec 5, 2016·Pharmacological Reports : PR·Marek CieślakMichał Komoszyński
Jun 7, 2020·Journal of Neurology, Neurosurgery, and Psychiatry·Didu KariyawasamMichelle Anne Farrar
Jun 19, 2021·Progress in Neurobiology·Edward BeamerTobias Engel

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