The Biochemistry and Epigenetics of Epilepsy: Focus on Adenosine and Glycine.
The Biochemistry and Epigenetics of Epilepsy: Focus on Adenosine and Glycine.
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DOI：
10.3389/fnmol.2016.00026
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发表时间：
2016
影响因子：
4.8
通讯作者：
Boison D
中科院分区：
文献类型：
--
作者：
Boison D
癫痫是最常见的神经系统疾病之一，表现为一种复杂的网络稳态紊乱，其特征是自发性非诱发性癫痫发作和相关合并症。目前使用的抗癫痫药物旨在抑制神经元过度兴奋，从而抑制癫痫发作。然而，目前的抗癫痫药物对超过30%的患者无效，不能影响癫痫的合并症，也不能阻止癫痫的发生和进展（癫痫发生）。预防癫痫及其进展仍然是癫痫研究和治疗开发的圣杯，需要新颖的概念进步来找到解决这一紧迫医疗需求的方法。癫痫发生的甲基化假说表明 DNA 甲基化的变化与疾病的进展有关。特别是，整体 DNA 高甲基化似乎与慢性癫痫有关。临床和实验证据表明，可以通过生化操作和针对先前未识别的有助于癫痫发展和维持癫痫状态的表观遗传功能的生化操作来预防癫痫及其进展。这篇小综述将讨论癫痫发生以及腺苷和甘氨酸之间的生化相互作用所涉及的表观遗传机制，作为理解生物化学适应不良变化作为癫痫发展的主要促成因素的贡献的概念进展。基于 DNA 甲基化组的生化操作的新发现表明：(i) 表观遗传机制在癫痫发生中发挥功能性作用； (ii)表观基因组的治疗性重建是一种有效的抗癫痫疗法。
Epilepsy, one of the most prevalent neurological conditions, presents as a complex disorder of network homeostasis characterized by spontaneous non-provoked seizures and associated comorbidities. Currently used antiepileptic drugs have been designed to suppress neuronal hyperexcitability and thereby to suppress epileptic seizures. However, the current armamentarium of antiepileptic drugs is not effective in over 30% of patients, does not affect the comorbidities of epilepsy, and does not prevent the development and progression of epilepsy (epileptogenesis). Prevention of epilepsy and its progression remains the Holy Grail for epilepsy research and therapy development, requiring novel conceptual advances to find a solution to this urgent medical need. The methylation hypothesis of epileptogenesis suggests that changes in DNA methylation are implicated in the progression of the disease. In particular, global DNA hypermethylation appears to be associated with chronic epilepsy. Clinical as well as experimental evidence demonstrates that epilepsy and its progression can be prevented by biochemical manipulations and those that target previously unrecognized epigenetic functions contributing to epilepsy development and maintenance of the epileptic state. This mini-review will discuss, epigenetic mechanisms implicated in epileptogenesis and biochemical interactions between adenosine and glycine as a conceptual advance to understand the contribution of maladaptive changes in biochemistry as a major contributing factor to the development of epilepsy. New findings based on biochemical manipulation of the DNA methylome suggest that: (i) epigenetic mechanisms play a functional role in epileptogenesis; and (ii) therapeutic reconstruction of the epigenome is an effective antiepileptogenic therapy.