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| Home > Publications Database > Monitoring α-synuclein multimerization in vivo. |
| Home > Publications Database > Monitoring α-synuclein multimerization in vivo. |
| Journal Article | DZNE-2020-06778 |
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2019
FASEB
Bethesda, Md.
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Please use a persistent id in citations: doi:10.1096/fj.201800148RRR
Abstract: 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.
Keyword(s): Amyloid: chemistry (MeSH) ; Animals (MeSH) ; Disease Models, Animal (MeSH) ; Drosophila melanogaster: growth & development (MeSH) ; Drosophila melanogaster: metabolism (MeSH) ; Male (MeSH) ; Phosphorylation (MeSH) ; Protein Multimerization (MeSH) ; Reactive Oxygen Species: metabolism (MeSH) ; Serine (MeSH) ; alpha-Synuclein: chemistry (MeSH) ; alpha-Synuclein: genetics (MeSH) ; alpha-Synuclein: metabolism (MeSH) ; Amyloid ; Reactive Oxygen Species ; alpha-Synuclein ; Serine
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