Activation of Mitochondrial Complex II-Dependent Respiration Is Beneficial for α-Synucleinopathies

Molecular Neurobiology
Christina FröhlichJens Pahnke

Abstract

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 mtRNA(Arg) 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 o...Continue Reading

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Citations

Aug 28, 2016·Acta Neuropathologica Communications·Johannes SteffenJens Pahnke
Jun 24, 2017·Acta Neuropathologica Communications·Johannes SteffenJens Pahnke
Jan 26, 2020·The FEBS Journal·Senthilkumar SivanesanJayakumar Rajadas
Feb 26, 2020·The Journal of Biological Chemistry·Marten SziborFrank N Gellerich

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Methods Mentioned

BETA
transgenic
ELISA
Enzyme-Linked

Software Mentioned

lmec
R
BZ Analyser
Datagraph Analysis
JMP
Pannoramic viewer
[UNK] prism
ScanDrop

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