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    Revisiting the role of neurotransmitters in epilepsy: An updated review. Akyuz Enes,Polat Ayse Kristina,Eroglu Ece,Kullu Irem,Angelopoulou Efthalia,Paudel Yam Nath Life sciences Epilepsy is a neurologicaldisorder characterized by persistent predisposition to recurrent seizurescaused by abnormal neuronal activity in the brain. Epileptic seizures maydevelop due to a relative imbalance of excitatory and inhibitory neurotransmitters. Expressional alterations of receptors and ion channelsactivated by neurotransmitters can lead to epilepsy pathogenesis. AIMS:In this updated comprehensive review, we discuss the emerging implication of mutations in neurotransmitter-mediated receptors and ion channels. We aim to provide critical findings of the current literature about the role of neurotransmitters in epilepsy. MATERIALS AND METHODS:A comprehensive literature review was conducted to identify and critically evaluate studies analyzing the possible relationship between epilepsy and neurotransmitters. The PubMed database was searched for related research articles. KEY FINDINGS:Glutamate and gamma-aminobutyric acid (GABA) are the main neurotransmitters playing a critical role in the pathophysiology of this balance, and irreversible neuronal damage may occur as a result of abnormal changes in these molecules. Acetylcholine (ACh), the main stimulant of the autonomic nervous system, mediates signal transmission through cholinergic and nicotinic receptors. Accumulating evidence indicates that dysfunction of nicotinic ACh receptors, which are widely expressed in hippocampal and cortical neurons, may be significantly implicated in the pathogenesis of epilepsy. The dopamine-norepinephrine-epinephrine cycle activates hormonal and neuronal pathways; serotonin, norepinephrine, histamine, and melatonin can act as both hormones and neurotransmitters. Recent reports have demonstrated that nitric oxide mediates cognitive and memory-related functions via stimulating neuronal transmission. SIGNIFICANCE:The elucidation of the role of the main mediators and receptors in epilepsy is crucial for developing new diagnostic and therapeutic approaches. 10.1016/j.lfs.2020.118826