In vivo demonstration that alpha-synuclein oligomers are toxic.

Winner B, Jappelli R, Maji SK, Desplats PA, Boyer L, Aigner S, Hetzer C, Loher T, Vilar M, Campioni S, Tzitzilonis C, Soragni A, Jessberger S, Mira H, Consiglio A, Pham E, Masliah E, Gage FH, Riek R (2011)

Publication Type: Journal article

Publication year: 2011

Journal

Proceedings of the National Academy of Sciences of the United States of America National Academy of Sciences

Book Volume: 108

Pages Range: 4194-9

Journal Issue: 10

DOI: 10.1073/pnas.1100976108

Abstract

The aggregation of proteins into oligomers and amyloid fibrils is characteristic of several neurodegenerative diseases, including Parkinson disease (PD). In PD, the process of aggregation of ?-synuclein (?-syn) from monomers, via oligomeric intermediates, into amyloid fibrils is considered the disease-causative toxic mechanism. We developed ?-syn mutants that promote oligomer or fibril formation and tested the toxicity of these mutants by using a rat lentivirus system to investigate loss of dopaminergic neurons in the substantia nigra. The most severe dopaminergic loss in the substantia nigra is observed in animals with the ?-syn variants that form oligomers (i.e., E57K and E35K), whereas the ?-syn variants that form fibrils very quickly are less toxic. We show that ?-syn oligomers are toxic in vivo and that ?-syn oligomers might interact with and potentially disrupt membranes.

Authors with CRIS profile

Beate Winner Professur für Stammzell-Modelle seltener neuraler Erkrankungen

Involved external institutions

Salk Institute for Biological Studies US United States (USA) (US) University of California, San Diego US United States (USA) (US) Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich CH Switzerland (CH)

How to cite

APA:

Winner, B., Jappelli, R., Maji, S.K., Desplats, P.A., Boyer, L., Aigner, S.,... Riek, R. (2011). In vivo demonstration that alpha-synuclein oligomers are toxic. Proceedings of the National Academy of Sciences of the United States of America, 108(10), 4194-9. https://doi.org/10.1073/pnas.1100976108

MLA:

Winner, Beate, et al. "In vivo demonstration that alpha-synuclein oligomers are toxic." Proceedings of the National Academy of Sciences of the United States of America 108.10 (2011): 4194-9.

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