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A reversible state ...
A reversible state of hypometabolism in a human cellular model of sporadic Parkinson's disease
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Schmidt, Sebastian (author)
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Stautner, Constantin (author)
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Vu, Duc Tung (author)
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Heinz, Alexander (author)
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Regensburger, Martin (author)
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Karayel, Ozge (author)
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Truembach, Dietrich (author)
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Artati, Anna (author)
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Kaltenhaeuser, Sabine (author)
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Nassef, Mohamed Zakaria (author)
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Hembach, Sina (author)
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Steinert, Letyfee (author)
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Winner, Beate (author)
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Juergen, Winkler (author)
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- Jastroch, Martin, 1977- (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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Luecken, Malte D. (author)
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Theis, Fabian J. (author)
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Westmeyer, Gil Gregor (author)
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Adamski, Jerzy (author)
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Mann, Matthias (author)
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Hiller, Karsten (author)
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Giesert, Florian (author)
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Weisenhorn, Daniela M. Vogt (author)
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Wurst, Wolfgang (author)
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Nature Communications. - 2041-1723. ; 14:1
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
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- 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 alpha-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. Mitochondrial dysfunction is a contributing factor in Parkinson's disease. Here the authors carry out a multilayered omics analysis of Parkinson's disease patient-derived neuronal cells, which reveals a reversible hypometabolism mediated by alpha-ketoglutarate dehydrogenase deficiency, which is correlated with disease progression in the donating patients.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Schmidt, Sebasti ...
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Stautner, Consta ...
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Vu, Duc Tung
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Heinz, Alexander
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Regensburger, Ma ...
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Karayel, Ozge
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show more...
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Truembach, Dietr ...
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Artati, Anna
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Kaltenhaeuser, S ...
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Nassef, Mohamed ...
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Hembach, Sina
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Steinert, Letyfe ...
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Winner, Beate
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Juergen, Winkler
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Jastroch, Martin ...
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Luecken, Malte D ...
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Theis, Fabian J.
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Westmeyer, Gil G ...
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Adamski, Jerzy
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Mann, Matthias
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Hiller, Karsten
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Giesert, Florian
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Weisenhorn, Dani ...
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Wurst, Wolfgang
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Nature Communica ...
- By the university
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Stockholm University