# Metabolomics of Multiple System Atrophy Patient-Derived Striatal Medium Spiny Neurons

## TL;DR

This study explores metabolic changes in neurons from multiple system atrophy patients, revealing mitochondrial dysfunction that could contribute to neurodegeneration.

## Contribution

The study identifies specific metabolic alterations in MSA patient-derived neurons, particularly in mitochondrial processes.

## Key findings

- MSA neurons show significantly lower levels of succinate and ATP compared to healthy controls.
- An imbalanced NAD+/NADH ratio was observed in MSA cell lines, indicating mitochondrial dysfunction.

## Abstract

In multiple system atrophy (MSA), the fatal movement disorder, cell populations of the striatum and other subcortical brain regions degenerate, leading to a rapidly progressive, atypical Parkinsonian syndrome. The pathophysiology of neurons and glial cells shows misfolding, aggregation, and increased release of the protein α-synuclein. In addition, neuronal hypoexcitability, a reduction in the activity of the mitochondrial respiratory chain, and a dysregulation of the enzymes involved in the biosynthesis of coenzyme Q10 were observed in human stem-cell models. In this study, untargeted and targeted metabolome analyses were performed with MSA patient-derived GABAergic striatal medium spiny neurons focusing on the citrate cycle and mitochondrial respiratory chain. The results indicate a significant decrease in succinate and ATP as well as an imbalanced NAD+/NADH ratio of MSA cell lines compared to matched healthy controls, suggesting alterations in mitochondrial processes which may facilitate neurodegeneration.