What is it about?
One-third of epileptic patients are drug refractory due to the limited efficacy of antiepileptic therapy. Thus, there is an immense need to find more effective, safer and well-tolerated antiepileptic drugs. A great deal of results suggests that adenosine (Ado), guanosine (Guo), inosine (Ino) or uridine (Urd) are endogenous antiepileptogenic modulators. Furthermore, nucleosides and their derivatives may be safe and effective potential drugs in the treatment of epilepsy. Conversely, nucleosidergic modulatory system implying nucleoside levels, metabolism, receptors and transporters may also be involved in seizure pathomechanisms. Application of Ado receptor agonists as well as antagonists, elevation of nucleoside levels (e.g., by nucleoside metabolism inhibitors, and Ado-releasing implants) or utilization of non-Ado nucleosides may also turn to be useful approaches to decrease epileptic activity. However, all drugs exerting their effects on the nucleosidergic modulatory system may affect the fine regulation of glia-neuron interactions that are intimately governed by various nucleosidergic processes. Perturbation of the complex, bidirectional communication between neurons and astrocytes through these nucleosidergic modulatory mechanisms may lead to pathological changes in the central nervous system (CNS) and therefore may cause significant side effects.
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Why is it important?
Deeper understanding of the nucleosidergic modulatory control over glia-neuron interactions is essential in order to develop more effective and safe nucleoside-based antiepileptic drugs.
Perspectives
Application of Ino, Guo and Urd can be considered a safer therapeutic approach since these nucleosides and their analogues are well tolerated with minor side effects. Nevertheless, modulation of glia-neuron interactions by way of nucleosidergic modulatory system may have the potential to not only improve epileptic condition, but also impairing it. Thus, when applying antiepileptic drugs effective on nucleosidergic modulatory system in different types of epilepsies, disclosure of specific regulatory mechanisms of glia-neuron interactions is required. As outlined above, emerging evidence suggest a role that the nucleosidergic modulatory system plays in epilepsy through interplaying astroglia and neurons. However, more detailed understanding of short- and long-range processes regulated by astroglia-specific nucleoside receptors and transporters is required. Investigation of alteration in glia-neuron coupling evoked by activation of the nucleosidergic modulatory system during epileptic discharges may induce novel drug discovery campaigns to develop more effective antiepileptic drugs with fewer side effects in the future.
Dr Zsolt Kovacs
Eötvös Loránd University
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This page is a summary of: Effects of Nucleosides on Glia - Neuron Interactions Open up New Vistas in the Development of More Effective Antiepileptic Drugs, Current Medicinal Chemistry, March 2015, Bentham Science Publishers,
DOI: 10.2174/0929867322666150212153210.
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