title: Effects of nucleosides on glia - neuron interactions open up new vistas in the development of more effective antiepileptic drugs.
abstract: 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 Adoreleasing 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. Thus, a 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. In this review article we focus on the role of Ado and Urd in glia-neuron interactions, placing emphasis on their implications for the treatment of epilepsy.
authors: Zsolt
authors: Z
authors: Kovacs
authors: Julianna
authors: J
authors: Kardos
authors: Katalin A
authors: KA
authors: Kekesi
authors: Gabor
authors: G
authors: Juhasz
authors: Renata
authors: R
authors: Lakatos
authors: Department of Zoology, University of West Hungary, Savaria Campus; Karolyi Gaspar ter 4., Szombathely, 9700 Hungary. zskovacs@ttk.nyme.hu.
authors: Laszlo
authors: L
authors: Heja
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009705:Nucleosides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010770:Phosphotransferases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D009705:Nucleosides; D010770:Phosphotransferases