Fuente: Biomolecules - Revista científica (MDPI) Biomolecules, Vol. 16, Pages 190: Metabolomics of Multiple System Atrophy Patient-Derived Striatal Medium Spiny Neurons
Biomolecules doi: 10.3390/biom16020190
Authors:
Nadine J. Smandzich
Heike Bähre
Thomas Gschwendtberger
Stephan Greten
Lan Ye
Martin Klietz
Alessio Di Fonzo
Lisa M. Henkel
Florian Wegner

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.