Christina Fröhlich, Katja Zschiebsch, Victoria Gröger, Kristin Paarmann, Johannes Steffen, Christoph Thurm, Eva-Maria Schropp, Thomas Brüning, Frank Norbert Gellerich, Martin Radloff, Rainer Schwabe, Ingolf Lachmann, Markus Krohn, Saleh Ibrahim, Jens Pahnke
- Parkinson’s disease and dementia with Lewy bodies are major challenges in research and clinical medicine world-wide and contribute to the most common neurodegenerative disorders. Previously, specific mitochondrial polymorphisms have been found to enhance clearance of amyloid-β from the brain of APP-transgenic mice leading to beneficial clinical outcome. It has been discussed whether specific mitochondrial alterations contribute to disease progression or even prevent toxic peptide deposition, as seen in many neurodegenerative diseases. Here, we investigated α-synuclein-transgenic C57BL/6J mice with the A30P mutation, and a novel A30P C57BL/6J mouse model with three mitochondrial DNA polymorphisms in the ND3, COX3 and mtRNAArg genes, as found in the inbred NOD/LtJ mouse strain. We were able to detect that the new model has increased mitochondrial complex II-respiration which occurs in parallel to neuronal loss and improved motor performance, although it exhibits higher amounts of high molecular weight species of α-synuclein. High molecular weight aggregates of different peptides are controversially discussed in the light of neurodegeneration. A favourable hypothesis states that high molecular weight species are protective and of minor importance for the pathogenesis of neurodegenerative disorders as compared to the extreme neurotoxic monomers and oligomers. Summarising, our results point to a potentially protective and beneficial effect of specific mitochondrial polymorphisms which cause improved mitochondrial complex II-respiration in α-synucleinopathies, an effect that could be exploited further for pharmaceutical interventions.
MetadatenAuthor: | Christina Fröhlich, Katja ZschiebschGND, Victoria Gröger, Kristin Paarmann, Johannes Steffen, Christoph Thurm, Eva-Maria Schropp, Thomas Brüning, Frank Norbert GellerichORCiDGND, Martin Radloff, Rainer Schwabe, Ingolf Lachmann, Markus Krohn, Saleh Ibrahim, Jens Pahnke |
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URN: | urn:nbn:de:hebis:30:3-456513 |
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DOI: | https://doi.org/10.1007/s12035-015-9399-4 |
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ISSN: | 1559-1182 |
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ISSN: | 0893-7648 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/26319560 |
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Parent Title (English): | Molecular neurobiology |
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Publisher: | Humana Press |
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Place of publication: | Totowa, NJ |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2015 |
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Date of first Publication: | 2015/08/29 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2018/02/13 |
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Tag: | Alpha-synuclein; Complex II; Mitochondria; Oxidative phosphorylation; Parkinson’s disease |
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Volume: | 53 |
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Issue: | 7 |
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Page Number: | 17 |
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First Page: | 4728 |
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Last Page: | 4744 |
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Note: | © The Author(s) 2015. Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
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HeBIS-PPN: | 428653138 |
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Institutes: | Biochemie, Chemie und Pharmazie / Pharmazie |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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