A reversible state of hypometabolism in a human cellular model of sporadic Parkinson’s disease

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

A reversible state of hypometabolism in a human cellular model of sporadic Parkinson’s disease. / Schmidt, Sebastian; Stautner, Constantin; Vu, Duc Tung; Heinz, Alexander; Regensburger, Martin; Karayel, Ozge; Trümbach, Dietrich; Artati, Anna; Kaltenhäuser, Sabine; Nassef, Mohamed Zakaria; Hembach, Sina; Steinert, Letyfee; Winner, Beate; Jürgen, Winkler; Jastroch, Martin; Luecken, Malte D.; Theis, Fabian J.; Westmeyer, Gil Gregor; Adamski, Jerzy; Mann, Matthias; Hiller, Karsten; Giesert, Florian; Vogt Weisenhorn, Daniela M.; Wurst, Wolfgang.

In: Nature Communications, Vol. 14, No. 1, 7674, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

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, Jürgen, W, Jastroch, M, Luecken, MD, Theis, FJ, Westmeyer, GG, Adamski, J, Mann, M, Hiller, K, Giesert, F, Vogt Weisenhorn, DM & Wurst, W 2023, 'A reversible state of hypometabolism in a human cellular model of sporadic Parkinson’s disease', Nature Communications, vol. 14, no. 1, 7674. https://doi.org/10.1038/s41467-023-42862-7

APA

Schmidt, S., Stautner, C., Vu, D. T., Heinz, A., Regensburger, M., Karayel, O., Trümbach, D., Artati, A., Kaltenhäuser, S., Nassef, M. Z., Hembach, S., Steinert, L., Winner, B., Jürgen, W., Jastroch, M., Luecken, M. D., Theis, F. J., Westmeyer, G. G., Adamski, J., ... Wurst, W. (2023). A reversible state of hypometabolism in a human cellular model of sporadic Parkinson’s disease. Nature Communications, 14(1), [7674]. https://doi.org/10.1038/s41467-023-42862-7

Vancouver

Schmidt S, Stautner C, Vu DT, Heinz A, Regensburger M, Karayel O et al. A reversible state of hypometabolism in a human cellular model of sporadic Parkinson’s disease. Nature Communications. 2023;14(1). 7674. https://doi.org/10.1038/s41467-023-42862-7

Author

Schmidt, Sebastian ; Stautner, Constantin ; Vu, Duc Tung ; Heinz, Alexander ; Regensburger, Martin ; Karayel, Ozge ; Trümbach, Dietrich ; Artati, Anna ; Kaltenhäuser, Sabine ; Nassef, Mohamed Zakaria ; Hembach, Sina ; Steinert, Letyfee ; Winner, Beate ; Jürgen, Winkler ; Jastroch, Martin ; Luecken, Malte D. ; Theis, Fabian J. ; Westmeyer, Gil Gregor ; Adamski, Jerzy ; Mann, Matthias ; Hiller, Karsten ; Giesert, Florian ; Vogt Weisenhorn, Daniela M. ; Wurst, Wolfgang. / A reversible state of hypometabolism in a human cellular model of sporadic Parkinson’s disease. In: Nature Communications. 2023 ; Vol. 14, No. 1.

Bibtex

@article{a631d2e48a6e4c0eb340ee1e6f2533e7,
title = "A reversible state of hypometabolism in a human cellular model of sporadic Parkinson{\textquoteright}s disease",
abstract = "Sporadic Parkinson{\textquoteright}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.",
author = "Sebastian Schmidt and Constantin Stautner and Vu, {Duc Tung} and Alexander Heinz and Martin Regensburger and Ozge Karayel and Dietrich Tr{\"u}mbach and Anna Artati and Sabine Kaltenh{\"a}user and Nassef, {Mohamed Zakaria} and Sina Hembach and Letyfee Steinert and Beate Winner and Winkler J{\"u}rgen and Martin Jastroch and Luecken, {Malte D.} and Theis, {Fabian J.} and Westmeyer, {Gil Gregor} and Jerzy Adamski and Matthias Mann and Karsten Hiller and Florian Giesert and {Vogt Weisenhorn}, {Daniela M.} and Wolfgang Wurst",
note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
doi = "10.1038/s41467-023-42862-7",
language = "English",
volume = "14",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - A reversible state of hypometabolism in a human cellular model of sporadic Parkinson’s disease

AU - Schmidt, Sebastian

AU - Stautner, Constantin

AU - Vu, Duc Tung

AU - Heinz, Alexander

AU - Regensburger, Martin

AU - Karayel, Ozge

AU - Trümbach, Dietrich

AU - Artati, Anna

AU - Kaltenhäuser, Sabine

AU - Nassef, Mohamed Zakaria

AU - Hembach, Sina

AU - Steinert, Letyfee

AU - Winner, Beate

AU - Jürgen, Winkler

AU - Jastroch, Martin

AU - Luecken, Malte D.

AU - Theis, Fabian J.

AU - Westmeyer, Gil Gregor

AU - Adamski, Jerzy

AU - Mann, Matthias

AU - Hiller, Karsten

AU - Giesert, Florian

AU - Vogt Weisenhorn, Daniela M.

AU - Wurst, Wolfgang

N1 - Publisher Copyright: © 2023, The Author(s).

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-023-42862-7

DO - 10.1038/s41467-023-42862-7

M3 - Journal article

C2 - 37996418

AN - SCOPUS:85177734756

VL - 14

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 7674

ER -

ID: 379170349