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获得性颞叶癫痫的分子遗传学。

Molecular Genetics of Acquired Temporal Lobe Epilepsy.

机构信息

Institute of Molecular and Cellular Anatomy, Ulm University, 89081 Ulm, Germany.

出版信息

Biomolecules. 2024 Jun 7;14(6):669. doi: 10.3390/biom14060669.

Abstract

An epilepsy diagnosis reduces a patient's quality of life tremendously, and it is a fate shared by over 50 million people worldwide. Temporal lobe epilepsy (TLE) is largely considered a nongenetic or acquired form of epilepsy that develops in consequence of neuronal trauma by injury, malformations, inflammation, or a prolonged (febrile) seizure. Although extensive research has been conducted to understand the process of epileptogenesis, a therapeutic approach to stop its manifestation or to reliably cure the disease has yet to be developed. In this review, we briefly summarize the current literature predominately based on data from excitotoxic rodent models on the cellular events proposed to drive epileptogenesis and thoroughly discuss the major molecular pathways involved, with a focus on neurogenesis-related processes and transcription factors. Furthermore, recent investigations emphasized the role of the genetic background for the acquisition of epilepsy, including variants of neurodevelopmental genes. Mutations in associated transcription factors may have the potential to innately increase the vulnerability of the hippocampus to develop epilepsy following an injury-an emerging perspective on the epileptogenic process in acquired forms of epilepsy.

摘要

癫痫诊断极大地降低了患者的生活质量,全世界有超过 5000 万人患有这种疾病。颞叶癫痫(TLE)被广泛认为是一种非遗传性或获得性癫痫,是由于神经元损伤、畸形、炎症或长时间(热性)发作引起的。尽管已经进行了广泛的研究来了解癫痫发生的过程,但尚未开发出一种治疗方法来阻止其表现或可靠地治愈这种疾病。在这篇综述中,我们主要基于兴奋性啮齿动物模型的数据,简要总结了目前的文献,讨论了驱动癫痫发生的细胞事件,并深入讨论了涉及的主要分子途径,重点关注神经发生相关过程和转录因子。此外,最近的研究强调了遗传背景在获得性癫痫中的作用,包括神经发育基因的变异。相关转录因子的突变可能具有内在的潜力,使海马体在受伤后更容易患上癫痫——这是对获得性癫痫中癫痫发生过程的一个新视角。

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