Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (2): 360-368.doi: 10.4103/1673-5374.379018

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Metabotropic glutamate receptors (mGluRs) in epileptogenesis: an update on abnormal mGluRs signaling and its therapeutic implications

Leyi Huang1, #, Wenjie Xiao1, #, Yan Wang1, Juan Li2, Jiaoe Gong3, Ewen Tu4, Lili Long2, Bo Xiao2, Xiaoxin Yan1, Lily Wan1, *   

  1. 1Department of Anatomy and Neurobiology, Central South University Xiangya Medical School, Changsha, Hunan Province, China; 2Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China; 3Department of Neurology, Hunan Children’s Hospital, Changsha, Hunan Province, China; 4Department of Neurology, Brain Hospital of Hunan Province, Changsha, Hunan Province, China
  • Online:2024-02-15 Published:2023-08-30
  • Contact: Lily Wan, MD, PhD, wanll1203@csu.edu.cn.
  • Supported by:
    This work was supported by the Natural Science Foundation of Hunan Province, No. 2021JJ30389 (to JG); the Key Research and Development Program of Hunan Province of China, Nos. 2022SK2042 (to LL) and 2020SK2122 (to ET). 

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Abstract: Epilepsy is a neurological disorder characterized by high morbidity, high recurrence, and drug resistance. Enhanced signaling through the excitatory neurotransmitter glutamate is intricately associated with epilepsy. Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors activated by glutamate and are key regulators of neuronal and synaptic plasticity. Dysregulated mGluR signaling has been associated with various neurological disorders, and numerous studies have shown a close relationship between mGluRs expression/activity and the development of epilepsy. In this review, we first introduce the three groups of mGluRs and their associated signaling pathways. Then, we detail how these receptors influence epilepsy by describing the signaling cascades triggered by their activation and their neuroprotective or detrimental roles in epileptogenesis. In addition, strategies for pharmacological manipulation of these receptors during the treatment of epilepsy in experimental studies is also summarized. We hope that this review will provide a foundation for future studies on the development of mGluR-targeted antiepileptic drugs.

Key words: antiepileptic drugs, epileptogenesis, metabotropic glutamate receptors (mGluRs), signal pathways, therapeutic potentials