The pathogenesis of epilepsy remains unclear; however, a prevailing hypothesis suggests that the primary underlying cause is an imbalance between neuronal excitability and inhibition. Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway, which is primarily involved in deoxynucleic acid synthesis and antioxidant defense mechanisms and exhibits increased expression during the chronic phase of epilepsy, predominantly colocalizing with neurons. G6PD overexpression significantly reduces the frequency and duration of spontaneous recurrent seizures. Furthermore, G6PD overexpression enhances signal transducer and activator of transcription 1 (STAT1) expression, thus influencing N-methyl--aspartic acid receptors expression, and subsequently affecting seizure activity. Importantly, the regulation of STAT1 by G6PD appears to be mediated primarily through reactive oxygen species signaling pathways. Collectively, our findings highlight the pivotal role of G6PD in modulating epileptogenesis, and suggest its potential as a therapeutic target for epilepsy.

中文翻译：

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6-磷酸葡萄糖脱氢酶通过抑制活性氧的产生来促进信号转导器和转录激活剂 1 介导的 N-甲基-d-天冬氨酸受体抑制，从而减轻癫痫发作


癫痫的发病机制尚不清楚；然而，一个普遍的假设表明，主要原因是神经元兴奋性和抑制性之间的不平衡。 6-磷酸葡萄糖脱氢酶（G6PD）是磷酸戊糖途径中的关键酶，主要参与脱氧核酸合成和抗氧化防御机制，并在癫痫慢性期表现出表达增加，主要与神经元共定位。 G6PD 过度表达显着降低自发性复发性癫痫发作的频率和持续时间。此外，G6PD 过表达会增强信号转导子和转录激活子 1 (STAT1) 的表达，从而影响 N-甲基-天冬氨酸受体的表达，进而影响癫痫发作活动。重要的是，G6PD 对 STAT1 的调节似乎主要通过活性氧信号通路介导。总的来说，我们的研究结果强调了 G6PD 在调节癫痫发生中的关键作用，并表明其作为癫痫治疗靶点的潜力。