Abstract
According to an update from the World Health Organization, approximately 50 million people worldwide suffer from epilepsy, and nearly one-third of these individuals are resistant to the currently available antiepileptic drugs, which has resulted in an insistent pursuit of novel strategies for seizure treatment. Recently, methylglyoxal (MG) was demonstrated to serve as a partial agonist of the gamma-aminobutyric acid type A (GABAA) receptor and to play an inhibitory role in epileptic activities. However, MG is also a substrate in the generation of advanced glycation end products (AGEs) that function by activating the receptor of AGEs (RAGE). The AGE/RAGE axis is responsible for the transduction of inflammatory cascades and appears to be an adverse pathway in epilepsy. This study systematically reviewed the significance of GABAergic MG, glyoxalase I (GLO1; responsible for enzymatic catalysis of MG cleavage) and downstream RAGE signaling in epilepsy. This work also discussed the potential of miRNAs that target multiple mRNAs and introduced a preliminary scheme for screening and validating miRNA candidates with the goal of reconciling the conflicting effects of MG for the future development of seizure treatments.
Highlights
Glucose is the most common form of carbohydrate and acts as an essential substrate for brain energy metabolism via glycolysis and subsequent aerobic respiration
This study systematically reviewed the significance of GABAergic MG, glyoxalase I (GLO1), which is responsible for the enzymatic catalysis of MG cleavage, and downstream receptor of AGEs (RAGE) signaling in epilepsy and discussed the potential of miRNAs with the goal of establishing groundwork for future research aiming to reconcile the conflicting effects of MG on epileptic seizures
The variation at rs1049346 is potentially useful for assessing the risk of late-onset and drug-resistant epilepsy (Tao et al, 2016). These findings suggest that inhibiting the enzymatic activity of GLO1 and reducing the clearance of GABAergic MG might be a novel approach for improving epileptic seizures
Summary
Glucose is the most common form of carbohydrate and acts as an essential substrate for brain energy metabolism via glycolysis and subsequent aerobic respiration. MG has been demonstrated to be a partial agonist of the gamma-aminobutyric acid type A receptor (GABAA) and plays an inhibitory role in epileptic activities (Distler et al, 2013). Clinical observations have indicated that carbohydrate-enriched food and drink are precipitating factors of epileptic seizures, and the antiepileptic effects of a ketogenic diet (which comprises high fat, adequate protein and low carbohydrate contents) have been confirmed in children with intractable epilepsy (Kossoff, 2004; Freitas et al, 2007; Luat et al, 2016). Other substances metabolized from carbohydrates most likely overwhelm the antiepileptic role of MG and shift the balance toward epileptic seizures
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