Xinqi Fang
Hong Jiang
Xiaobing Zhang
Longbo Zhang- 1Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
- 2Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
- 3Department of Psychology, Florida State University, Tallahassee, FL, United States
- 4Departments of Neurosurgery, and Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT, United States
Editorial on the Research Topic
mTOR pathway malfunctions in neurodevelopmental disorders
The Mechanistic Target of Rapamycin (mTOR) pathway integrates a variety of intracellular and extracellular signaling and coordinates many essential cellular processes, including protein synthesis and autophagy. During the neurodevelopment, mTOR acts as one of the main directors controlling the differentiation and proliferation of neural progenitor cells, neuronal morphology and migration, and synaptic plasticity (Costa-Mattioli and Monteggia, 2013). Malfunctions of mTOR signaling have been implicated across the continuum of neurodevelopmental and neuropsychiatric disorders (Nguyen and Bordey, 2021). mTORopathies such as tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD), are characterized by hyperactivation of mTOR signaling, malformation of cortical development, and disruptions of neural circuits and brain network leading to intractable epilepsy and cognition and behavior deficits (Crino, 2015). During last decades, extensive efforts on the mechanism studies have improved our understandings of the precise roles of mTOR involved in neurodevelopment and associated neurological disorders, and have promoted the development of targeted therapies.
In this Research Topic, a diverse insight into the different areas of research aimed at better understanding of neurological disorders caused by mTOR dysregulation. The original research by Riley et al. investigated the effects of mTOR on the development of inhibitory granule cells by generating a hyperactive mTOR complex 1 (mTORC1) model induced by homozygous Tsc2 mutant. These results demonstrate that Tsc2 has a critical role in regulating neural development and shapes inhibitory granule cells molecular and morphological characteristics. In addition, they performed a transcriptome profiling revealing a significantly different expression in the gene networks regulating neural circuitry following the loss of Tsc2 gene. Ouyang et al. assessed GWAS data of epilepsy from the International League Against Epilepsy and gut microbiota from MiBioGen, and applied Mendelian Randomization analysis to explore the potential causal relationship among the gut microbiota, metabolites, and epilepsy. The study allows to explore the etiology of epilepsy from a new dimension. In the review articles, Girodengo et al. summarized the accumulating evidence from single-cell transcriptomics and cerebral organoid-based studies to improve our understanding of the crucial role of mTOR pathway in brain development and neurological disorders. Furthermore, they highlighted new ultra-sensitive techniques for the identification of somatic mTOR pathway mutations shedding light on the neurodevelopmental origin and phenotypic heterogeneity in mTORopathy patients. Wang et al. reviewed the current advances in imaging genetics in brain microcircuits and epileptic networks during brain development. The imaging genetics analysis accurately and efficiently integrates multidimensional datasets within a unified framework, providing a unique opportunity to generate a global vision for epilepsy to promote the molecular mechanism exploration and develop targeted treatment strategies.
In summary, the present Research Topic comprises original research and comprehensive reviews highlighting the role of mTOR signaling in neurodevelopment disorders. We hope that this topic will inspire further mechanism exploration of mTOR with the aim of fully restoring function to those neurological disorders.
Author contributions
All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.
Acknowledgments
We thank all authors for their contribution to this Research Topic and we would like also to acknowledge the work of reviewers whose constructive comments contributed to improve the quality of the articles.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note
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References
Costa-Mattioli, M., and Monteggia, L. M. (2013). mTOR complexes in neurodevelopmental and neuropsychiatric disorders. Nat. Neurosci. (2013) 16, 153715–43. doi: 10.1038/nn.3546
Crino, P. B. (2015). mTOR signaling in epilepsy: insights from malformations of cortical development. Cold Spring Harb. Perspect. Med. (2015) 5:a022442. doi: 10.1101/cshperspect.a022442
Keywords: mTOR, neurodevelopmental disorders, epilepsy, microbiota, genomics
Citation: Fang X, Jiang H, Zhang X and Zhang L (2023) Editorial: mTOR pathway malfunctions in neurodevelopmental disorders. Front. Mol. Neurosci. 16:1131002. doi: 10.3389/fnmol.2023.1131002
Received: 24 December 2022; Accepted: 02 January 2023;
Published: 17 January 2023.
Edited and reviewed by: Clive R. Bramham, University of Bergen, Norway
Copyright © 2023 Fang, Jiang, Zhang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Longbo Zhang, 
longbo.zhang@yale.edu