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Advanced Neurology

REVIEW ARTICLE
mTOR inhibition in epilepsy: A literature review

Lip-Yuen Teng * , Min Jung Chang 2,3,4 , and Se Hee Kim *
1
5
1 Pediatric Neurology, Department of Pediatrics, Hospital Tuanku Ja’afar, Seremban, Malaysia
2 Department of Pharmacy and Yonsei Institute of Pharmaceutical Science, College of Pharmacy,
Yonsei University, Incheon, Republic of Korea
3 Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and
Pharmacy, Yonsei University, Incheon, Republic of Korea
4 Graduate Program of Industrial Pharmaceutical Science, Yonsei University, Incheon, Republic of
Korea
5 Pediatric Neurology, Department of Pediatrics, Yonsei University College of Medicine, Epilepsy
Research Institute, Severance Children’s Hospital, Seoul, Republic of Korea
(This article belongs to the Special Issue: Advances in the pathogenesis, diagnosis and treatment
of epilepsy)

Abstract

Hyperactivation of the mammalian target of the rapamycin (mTOR) pathway
causes epilepsies, neurodevelopmental disorders, and malformations of cortical
development, collectively known as mTORopathies. These conditions arise from
loss-of-function variants in negative regulators or gain-of-function variants in
positive regulators of the mTOR pathway. Conventional antiseizure medications
mainly target downstream effectors such as ion channels or neurotransmitter
activity to suppress seizures. On the contrary, extensive pre-clinical and clinical
*Corresponding authors: evidence has demonstrated that mTOR inhibitors have anti-epileptogenic or disease-
Se Hee Kim modifying effects, potentially preventing epilepsy or slowing disease progression
(seheekim@yuhs.ac)
Lip-Yuen Teng rather than merely controlling seizures. In general, mTOR inhibitors bind to mTOR
(lyteng92@gmail.com) protein, preventing its interactions with substrates and disrupting mTOR complex
assembly, thereby suppressing downstream activities. In this review, we provide a
Citation: Teng LY, Chang MJ,
Kim SH. mTOR inhibition in comprehensive overview of the mTOR signaling pathway, outline the spectrum of
epilepsy: A literature review. mTORopathies and its subset (GATORopathies), and highlight the clinical applications
Adv Neuro. 2024;3(3):3568. of mTOR inhibitors, particularly everolimus, along with other potential mTOR-
doi: 10.36922/an.3568
modulating agents.
Received: May 3, 2024
Accepted: June 19, 2024 Keywords: mTOR; Epilepsy; Tuberous sclerosis; Rapamycin; Everolimus
Published Online: August 29, 2024
Copyright: © 2024 Author(s).
This is an Open-Access article
distributed under the terms of the 1. Introduction
Creative Commons Attribution
License, permitting distribution, Epilepsy contributes significantly to the global disease burden, particularly in children,
and reproduction in any medium, 1
provided the original work is accounting for 13.5 million disability-adjusted life years. Since 1850, antiseizure
properly cited. medications have been introduced to suppress seizure activity, primarily by targeting
2,3
Publisher’s Note: AccScience the balance between inhibitory and excitatory neurotransmission. D’Antuono
Publishing remains neutral with et al. observed that while antiseizure medications effectively controlled epileptiform
4
regard to jurisdictional claims in
published maps and institutional synchronization and aborted seizures, interictal epileptiform activity often remained
affiliations. notoriously resistant, raising concerns about their potential negative impact on

Volume 3 Issue 3 (2024) 1 doi: 10.36922/an.3568