2. Academic Validation
  3. Glucose-6-phosphate dehydrogenase alleviates epileptic seizures by repressing reactive oxygen species production to promote signal transducer and activator of transcription 1-mediated N-methyl-d-aspartic acid receptors inhibition

Glucose-6-phosphate dehydrogenase alleviates epileptic seizures by repressing reactive oxygen species production to promote signal transducer and activator of transcription 1-mediated N-methyl-d-aspartic acid receptors inhibition

  • Redox Biol. 2024 Aug:74:103236. doi: 10.1016/j.redox.2024.103236.
Liqin Hu 1,  Yan Liu 1,  Ziwei Yuan 1,  Haokun Guo 1,  Ran Duan 1,  Pingyang Ke 1,  Yuan Meng 1,  Xin Tian 2,  Fei Xiao 3
Affiliations

Affiliations

  • 1 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Major Neurological and Mental Disorders, Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, China.
  • 2 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Major Neurological and Mental Disorders, Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, China; Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, Chongqing, 400016, China. Electronic address: xintian@cqmu.edu.cn.
  • 3 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Major Neurological and Mental Disorders, Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, China; Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, Chongqing, 400016, China. Electronic address: feixiao81@126.com.
PMID: 38875958 DOI: 10.1016/j.redox.2024.103236
Abstract

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-d-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.

Keywords

Epilepsy; G6PD; Reactive oxygen species; STAT1.

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