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Monitoring α-synuclein multimerization in vivo

Lookup NU author(s): Professor Tiago Outeiro

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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.


Publication metadata

Author(s): Prasad V, Wasser Y, Hans F, Goswami A, Katona I, Outeiro TF, Kahle PJ, Schulz JB, Voigt A

Publication type: Article

Publication status: Published

Journal: The FASEB Journal

Year: 2019

Volume: 33

Issue: 2

Pages: 2116-2131

Print publication date: 01/02/2019

Online publication date: 30/01/2019

Acceptance date: 27/08/2018

ISSN (print): 0892-6638

ISSN (electronic): 1530-6860

Publisher: Federation of American Societies for Experimental Biology

URL: https://doi.org/10.1096/fj.201800148RRR

DOI: 10.1096/fj.201800148RRR

PubMed id: 30252534


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