Department of Anatomy, School of Biomedical Sciences, Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand.
Int J Mol Sci. 2024 Sep 11;25(18):9821. doi: 10.3390/ijms25189821.
Understanding the molecular mechanisms underlying the generation of absence seizures is crucial for developing effective, patient-specific treatments for childhood absence epilepsy (CAE). Currently, one-third of patients remain refractive to the antiseizure medications (ASMs), previously called antiepileptic drugs (AEDs), available to treat CAE. Additionally, these ASMs often produce serious side effects and can even exacerbate symptoms in some patients. Determining the precise cellular and molecular mechanisms directly responsible for causing this type of epilepsy has proven challenging as they appear to be complex and multifactorial in patients with different genetic backgrounds. Aberrant neuronal activity in CAE may be caused by several mechanisms that are not fully understood. Thus, dissecting the causal factors that could be targeted in the development of precision medicines without side effects remains a high priority and the ultimate goal in this field of epilepsy research. The aim of this review is to highlight our current understanding of potential causative mechanisms for absence seizure generation, based on the latest research using cutting-edge technologies. This information will be important for identifying potential targets for future therapeutic intervention.
了解失神发作产生的分子机制对于开发针对儿童失神性癫痫(CAE)的有效、个体化治疗方法至关重要。目前,三分之一的患者对以前用于治疗 CAE 的抗癫痫药物(ASM),即抗癫痫药物(AED)仍然没有反应。此外,这些 ASM 通常会产生严重的副作用,甚至在某些患者中加重症状。确定导致这种类型癫痫的确切细胞和分子机制具有挑战性,因为它们在具有不同遗传背景的患者中似乎是复杂和多因素的。CAE 中的异常神经元活动可能由几种机制引起,这些机制尚未完全了解。因此,在开发无副作用的精准医学中,剖析可能成为目标的因果因素仍然是该癫痫研究领域的首要任务和最终目标。本综述的目的是基于最新的使用尖端技术的研究,强调我们对失神发作产生的潜在因果机制的理解。这些信息对于确定未来治疗干预的潜在靶点非常重要。