Monitoring α‐synuclein multimerization in vivo
| العنوان: | Monitoring α‐synuclein multimerization in vivo |
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| المؤلفون: | Joerg B. Schulz, Philipp J. Kahle, Istvan Katona, Yasmine Wasser, Anand Goswami, Tiago F. Outeiro, Vibha Prasad, Aaron Voigt, Friederike Hans |
| المصدر: | The FASEB journal 33(2), 2116-2131 (2018). doi:10.1096/fj.201800148RRR |
| بيانات النشر: | Wiley, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Amyloid, Parkinson's disease, animal diseases, Protein aggregation, environment and public health, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Bimolecular fluorescence complementation, 0302 clinical medicine, In vivo, ddc:570, metabolism [Drosophila melanogaster], Serine, Genetics, medicine, chemistry [Amyloid], Animals, metabolism [Reactive Oxygen Species], metabolism [alpha-Synuclein], Phosphorylation, Molecular Biology, biology, Chemistry, Rotenone, biology.organism_classification, medicine.disease, nervous system diseases, Cell biology, Disease Models, Animal, Drosophila melanogaster, 030104 developmental biology, Proteostasis, chemistry [alpha-Synuclein], nervous system, genetics [alpha-Synuclein], alpha-Synuclein, health occupations, growth & development [Drosophila melanogaster], Protein Multimerization, Reactive Oxygen Species, 030217 neurology & neurosurgery, Biotechnology |
| الوصف: | 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. |
| تدمد: | 1530-6860 0892-6638 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::54a7b50613981fe877563d0c69c3a021Test https://doi.org/10.1096/fj.201800148rrrTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....54a7b50613981fe877563d0c69c3a021 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15306860 08926638 |
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