A reversible state of hypometabolism in a human cellular model of sporadic Parkinson’s disease
Schmidt S, Stautner C, Vu DT, Heinz A, Regensburger M, Karayel O, Trümbach D, Artati A, Kaltenhäuser S, Nassef MZ, Hembach S, Steinert L, Winner B, Winkler J, Jastroch M, Luecken MD, Theis FJ, Westmeyer GG, Adamski J, Mann M, Hiller K, Giesert F, Vogt Weisenhorn DM, Wurst W (2023)
Publication Type: Journal article
Publication year: 2023
Journal
Book Volume: 14
Article Number: 7674
Journal Issue: 1
DOI: 10.1038/s41467-023-42862-7
Abstract
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. A follow-up study of the patients approximately 10 years after initial biopsy demonstrated a correlation between OGDHC activity in our cellular model and the disease progression. In addition, the alterations in cellular metabolism observed in our cellular model were restored by interfering with the enhanced SHH signal transduction in sPD. Thus, inhibiting overactive SHH signaling may have potential as neuroprotective therapy during early stages of sPD.
Authors with CRIS profile
Martin Regensburger
Department of Molecular Neurology
Beate Winner
Professur für Stammzell-Modelle seltener neuraler Erkrankungen
Jürgen Winkler
Professur für Molekulare Neurologie
Involved external institutions
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Max-Planck-Institut für Biochemie / Max Planck Institute of Biochemistry
Germany (DE)
Technische Universität Braunschweig
Germany (DE)
Stockholm University / Stockholms universitet
Sweden (SE)
Technische Universität München (TUM)
Germany (DE)
Germany (DE)
Max-Planck-Institut für Biochemie / Max Planck Institute of Biochemistry
Germany (DE)
Technische Universität Braunschweig
Germany (DE)
Stockholm University / Stockholms universitet
Sweden (SE)
Technische Universität München (TUM)
Germany (DE)
How to cite
APA:
Schmidt, S., Stautner, C., Vu, D.T., Heinz, A., Regensburger, M., Karayel, O.,... Wurst, W. (2023). A reversible state of hypometabolism in a human cellular model of sporadic Parkinson’s disease. Nature Communications, 14(1). https://doi.org/10.1038/s41467-023-42862-7
MLA:
Schmidt, Sebastian, et al. "A reversible state of hypometabolism in a human cellular model of sporadic Parkinson’s disease." Nature Communications 14.1 (2023).
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