Berger Toni Christoph, Taubøll Erik, Heuser Kjell
Department of Neurology, Oslo University Hospital, Oslo, Norway.
Faculty of Medicine, University of Oslo, Oslo, Norway.
Front Cell Neurosci. 2022 Jul 22;16:931356. doi: 10.3389/fncel.2022.931356. eCollection 2022.
Pharmacological therapy of epilepsy has so far been limited to symptomatic treatment aimed at neuronal targets, with the result of an unchanged high proportion of patients lacking seizure control. The dissection of the intricate pathological mechanisms that transform normal brain matter to a focus for epileptic seizures-the process of epileptogenesis-could yield targets for novel treatment strategies preventing the development or progression of epilepsy. While many pathological features of epileptogenesis have been identified, obvious shortcomings in drug development are now believed to be based on the lack of knowledge of molecular upstream mechanisms, such as DNA methylation (DNAm), and as well as a failure to recognize glial cell involvement in epileptogenesis. This article highlights the potential role of DNAm and related gene expression (GE) as a treatment target in epileptogenesis.
迄今为止,癫痫的药物治疗仅限于针对神经元靶点的对症治疗,结果是仍有很大比例的患者癫痫发作得不到控制。剖析将正常脑组织转变为癫痫发作病灶的复杂病理机制(即癫痫发生过程),可能会为预防癫痫发展或进展的新治疗策略提供靶点。虽然已经确定了癫痫发生的许多病理特征,但目前认为药物开发存在明显缺陷是由于缺乏对分子上游机制(如DNA甲基化)的了解,以及未能认识到神经胶质细胞在癫痫发生中的作用。本文重点介绍了DNA甲基化及相关基因表达作为癫痫发生治疗靶点的潜在作用。