TY  - JOUR
A1  - Fröhlich, Christina
A1  - Zschiebsch, Katja
A1  - Gröger, Victoria
A1  - Paarmann, Kristin
A1  - Steffen, Johannes
A1  - Thurm, Christoph
A1  - Schropp, Eva-Maria
A1  - Brüning, Thomas
A1  - Gellerich, Frank Norbert
A1  - Radloff, Martin
A1  - Schwabe, Rainer
A1  - Lachmann, Ingolf
A1  - Krohn, Markus
A1  - Ibrahim, Saleh
A1  - Pahnke, Jens
T1  - Activation of Mitochondrial complex II-dependent respiration is beneficial for α-Synucleinopathies
T2  - Molecular neurobiology
N2  - 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.
KW  - Alpha-synuclein
KW  - Parkinson’s disease
KW  - Mitochondria
KW  - Complex II
KW  - Oxidative phosphorylation
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45651
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-456513
SN  - 1559-1182
SN  - 0893-7648
N1  - © 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.
VL  - 53
IS  - 7
SP  - 4728
EP  - 4744
PB  - Humana Press
CY  - Totowa, NJ
ER  -