核苷对神经胶质-神经元的交互作用开辟更高效抗癫痫药物发展的新远景

Title:Effects of Nucleosides on Glia - Neuron Interactions Open up New Vistas in the Development of More Effective Antiepileptic Drugs

Volume: 22 Issue: 12

Author(s): Zsolt Kovacs, Julianna Kardos, Katalin A. Kekesi, Gabor Juhasz, Renata Lakatos and Laszlo Heja

Affiliation:

关键词: 癫痫治疗，神经胶质，神经元，核苷。

摘要: 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.

Cite this article as:

Zsolt Kovacs, Julianna Kardos, Katalin A. Kekesi, Gabor Juhasz, Renata Lakatos and Laszlo Heja , Effects of Nucleosides on Glia - Neuron Interactions Open up New Vistas in the Development of More Effective Antiepileptic Drugs, Current Medicinal Chemistry 2015; 22 (12) . https://dx.doi.org/10.2174/0929867322666150212153210