REVIEW article
Front. Neurosci.
Sec. Neuropharmacology
Metabolic changes in mTOR pathway-associated cortical malformation
School of Medicine, University of Maryland, Baltimore, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Abstract
Malformations of cortical development (MCD) are a common cause of epilepsy, autism spectrum disorder (ASD), and intellectual disability (ID). A unifying mechanistic etiology for epilepsy, ASD, and ID has not been found due, in part, to the heterogeneity of MCD subtypes. However, changes in brain metabolism within MCD have emerged as a possible convergent mechanism across MCD that may have therapeutic potential. While there have been efforts to comprehensively describe known metabolic changes in other neurodevelopmental disorders, no such effort exists for MCD associated with mTOR pathway gene mutations (the most common cause of MCD; mTORopathies'). In this review, we detail finding related to mTORopathies that relate to dysfunctional brain metabolism including abnormal changes in macromolecule processing and mitochondrial metabolism. Further, we discuss cellular and molecular metabolic processes that may serve as key pathways in the development of MCD in utero and that may ultimately produce common mTORopathy phenotypes and sustain abnormal brain activity post-development.
Summary
Keywords
braindevelopment, developmental delay, Epilepsy, Intellectual Disability, Neurodevelopmental disorders, Seizures
Received
16 October 2025
Accepted
30 January 2026
Copyright
© 2026 Biswas and Iffland II. 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) or licensor 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: Philip Henry Iffland II
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.