Advances in the mTOR signaling pathway and its inhibitor rapamycin in epilepsy

• Published in: Brain and behavior Vol. 13; no. 6; pp. e2995 - n/a
• Main Authors: Zhao, Wei, Xie, Cong, Zhang, Xu, Liu, Ju, Liu, Jinzhi, Xia, Zhangyong
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.06.2023; John Wiley and Sons Inc; Wiley
• Subjects: Animals; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Autophagy; Brain research; Cell growth; Convulsions & seizures; Disease; Dopamine; Drug therapy; Epilepsy; Epilepsy - complications; Humans; Kinases; Metabolism; Morphology; mTOR; MTOR Inhibitors; Nervous system; Neural networks; Neurons; Pathogenesis; Physiology; Proteins; Quality of Life; rapamycin; Review; Reviews; Seizures - complications; Signal Transduction; signaling pathway; Sirolimus - pharmacology; Sirolimus - therapeutic use; TOR Serine-Threonine Kinases - antagonists & inhibitors; TOR Serine-Threonine Kinases - metabolism; epilepsy; mTOR; signaling pathway; rapamycin
• ISSN: 2162-3279; 2162-3279
• DOI: 10.1002/brb3.2995

Introduction Epilepsy is one of the most common and serious brain syndromes and has adverse consequences on a patient's neurobiological, cognitive, psychological, and social wellbeing, thereby threatening their quality of life. Some patients with epilepsy experience poor treatment effects due to the unclear pathophysiological mechanisms of the syndrome. Dysregulation of the mammalian target of the rapamycin (mTOR) pathway is thought to play an important role in the onset and progression of some epilepsies. Methods This review summarizes the role of the mTOR signaling pathway in the pathogenesis of epilepsy and the prospects for the use of mTOR inhibitors. Results The mTOR pathway functions as a vital mediator in epilepsy development through diverse mechanisms, indicating that the it has great potential as an effective target for epilepsy therapy. The excessive activation of mTOR signaling pathway leads to structural changes in neurons, inhibits autophagy, exacerbates neuron damage, affects mossy fiber sprouting, enhances neuronal excitability, increases neuroinflammation, and is closely associated with tau upregulation in epilepsy. A growing number of studies have demonstrated that mTOR inhibitors exhibit significant antiepileptic effects in both clinical applications and animal models. Specifically, rapamycin, a specific inhibitor of TOR, reduces the intensity and frequency of seizures. Clinical studies in patients with tuberous sclerosis complex have shown that rapamycin has the function of reducing seizures and improving this disease. Everolimus, a chemically modified derivative of rapamycin, has been approved as an added treatment to other antiepileptic medicines. Further explorations are needed to evaluate the therapeutic efficacy and application value of mTOR inhibitors in epilepsy. Conclusions Targeting the mTOR signaling pathway provides a promising prospect for the treatment of epilepsy. The regulation of the mTOR pathway provides a potential strategy for the treatment and prevention of epilepsy.