Winner, Beate ; Jappelli, Roberto ; Maji, Samir K. ; Desplats, Paula A. ; Boyer, Leah ; Aigner, Stefan ; Hetzer, Claudia ; Loher, Thomas ; Vilar, Marçal ; Campioni, Silvia ; Tzitzilonis, Christos ; Soragni, Alice ; Jessberger, Sebastian ; Mira, Helena ; Consiglio, Antonella ; Pham, Emiley ; Masliah, Eliezer ; Gage, Fred H. ; Riek, Roland (2011) In vivo demonstration that α-synuclein oligomers are toxic Proceedings of the National Academy of Sciences, 108 (10). pp. 4194-4199. ISSN 0027-8424
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Official URL: http://doi.org/10.1073/pnas.1100976108
Related URL: http://dx.doi.org/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 α-synuclein (α-syn) from monomers, via oligomeric intermediates, into amyloid fibrils is considered the disease-causative toxic mechanism. We developed α-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 α-syn variants that form oligomers (i.e., E57K and E35K), whereas the α-syn variants that form fibrils very quickly are less toxic. We show that α-syn oligomers are toxic in vivo and that α-syn oligomers might interact with and potentially disrupt membranes.
| Item Type: | Article |
|---|---|
| Source: | Copyright of this article belongs to National Academy of Science |
| ID Code: | 126551 |
| Deposited On: | 31 Oct 2022 04:22 |
| Last Modified: | 31 Oct 2022 04:22 |
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