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FASEB J. 2019 Feb;33(2):2116-2131. doi: 10.1096/fj.201800148RRR. Epub 2018 Sep 25.

Monitoring α-synuclein multimerization in vivo.

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Department of Neurology, University Medical Center, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany.
Laboratory of Functional Neurogenetics, Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, German Center for Neurodegenerative Diseases, Tübingen, Germany.
Institute of Neuropathology, University Medical Center, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany.
Department of Experimental Neurodegeneration, Center of Molecular Physiology of the Brain, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany.
Max Planck Institute for Experimental Medicine, Göttingen, Germany.
Institute of Neuroscience, The Medical School, Newcastle University, Newcastle Upon Tyne, United Kingdom; and.
Jülich-Aachen Research Alliance (JARA)-Brain Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH and Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany.


The pathophysiology of Parkinson's disease is characterized by the abnormal accumulation of α-synuclein (α-Syn), eventually resulting in the formation of Lewy bodies and neurites in surviving neurons in the brain. Although α-Syn aggregation has been extensively studied in vitro, there is limited in vivo knowledge on α-Syn aggregation. Here, we used the powerful genetics of Drosophila melanogaster and developed an in vivo assay to monitor α-Syn accumulation by using a bimolecular fluorescence complementation assay. We found that both genetic and pharmacologic manipulations affected α-Syn accumulation. Interestingly, we also found that alterations in the cellular protein degradation mechanisms strongly influenced α-Syn accumulation. Administration of compounds identified as risk factors for Parkinson's disease, such as rotenone or heavy metal ions, had only mild or even no impact on α-Syn accumulation in vivo. Finally, we show that increasing phosphorylation of α-Syn at serine 129 enhances the accumulation and toxicity of α-Syn. Altogether, our study establishes a novel model to study α-Syn accumulation and illustrates the complexity of manipulating proteostasis in vivo.-Prasad, V., Wasser, Y., Hans, F., Goswami, A., Katona, I., Outeiro, T. F., Kahle, P. J., Schulz, J. B., Voigt, A. Monitoring α-synuclein multimerization in vivo.


BiFC; Parkinson’s disease; protein aggregation; synucleinopathy


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