Sebastian Schmidt, Constantin Stautner, Duc Tung Vu, Alexander Heinz, Martin Regensburger, Ozge Karayel, Dietrich Trümbach, Anna Artati, Sabine Kaltenhäuser, Mohamed Zakaria Nassef, Sina Hembach, Letyfee Steinert, Beate Winner, Winkler Jürgen, Martin Jastroch, Malte D Luecken, Fabian J Theis, Gil Gregor Westmeyer, Jerzy Adamski, Matthias Mann, Karsten Hiller, Florian Giesert, Daniela M Vogt Weisenhorn, Wolfgang Wurst
Sporadic Parkinson's Disease (sPD) is a progressive neurodegenerative disorder caused by multiple genetic and environmental factors. Mitochondrial dysfunction is one contributing factor, but its role at different stages of disease progression is not fully understood. Here, we showed that neural precursor cells and dopaminergic neurons derived from induced pluripotent stem cells (hiPSCs) from sPD patients exhibited a hypometabolism. Further analysis based on transcriptomics, proteomics, and metabolomics identified the citric acid cycle, specifically the α-ketoglutarate dehydrogenase complex (OGDHC), as bottleneck in sPD metabolism...
November 23, 2023: Nature Communications