# Metabolic changes in mTOR pathway-associated cortical malformation

## TL;DR

This review explores how metabolic changes in the mTOR pathway may contribute to brain development disorders and their associated conditions like epilepsy and autism.

## Contribution

The paper provides a comprehensive overview of metabolic changes in mTORopathies, a common cause of cortical malformations.

## Key findings

- mTORopathies are linked to dysfunctional brain metabolism, including macromolecule processing issues.
- Abnormal mitochondrial metabolism is a key feature in mTOR pathway-associated cortical malformations.
- Metabolic processes may underlie common mTORopathy phenotypes and sustain abnormal brain activity.

## 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.