Monitoring α‐synuclein multimerization in vivo

Autor: Joerg B. Schulz, Philipp J. Kahle, Istvan Katona, Yasmine Wasser, Anand Goswami, Tiago F. Outeiro, Vibha Prasad, Aaron Voigt, Friederike Hans
Rok vydání: 2018
Předmět:
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
Zdroj: The FASEB journal 33(2), 2116-2131 (2018). doi:10.1096/fj.201800148RRR
ISSN: 1530-6860
0892-6638
DOI: 10.1096/fj.201800148rrr
Popis: 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.
Databáze: OpenAIRE
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