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Off-pathway α-synuclein oligomers seem to alter α-synuclein turnover in a cell model but lack seeding capability in vivo

Lookup NU author(s): Professor Tiago Outeiro

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Abstract

Aggregated α-synuclein is the major component of Lewy bodies, protein inclusions observed in the brain in neurodegenerative disorders such as Parkinson's disease and dementia with Lewy bodies. Experimental evidence indicates that α-synuclein potentially can be transferred between cells and act as a seed to accelerate the aggregation process. Here, we investigated in vitro and in vivo seeding effects of α-synuclein oligomers induced by the reactive aldehyde 4-oxo-2-nonenal (ONE). As measured by a Thioflavin-T based fibrillization assay, there was an earlier onset of aggregation when α-synuclein oligomers were added to monomeric α-synuclein. In contrast, exogenously added α-synuclein oligomers did not induce aggregation in a cell model. However, cells overexpressing α-synuclein that were treated with the oligomers displayed reduced α-synuclein levels, indicating that internalized oligomers either decreased the expression or accelerated the degradation of transfected α-synuclein. Also in vivo there were no clear seeding effects, as intracerebral injections of α-synuclein oligomers into the neocortex of α-synuclein transgenic mice did not induce formation of proteinase K resistant α-synuclein pathology. Taken together, we could observe a seeding effect of the ONE-induced α-synuclein oligomers in a fibrillization assay, but neither in a cell nor in a mouse model. © 2013 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted.


Publication metadata

Author(s): Fagerqvist T, Nasstrom T, Ihse E, Lindstrom V, Sahlin C, Fangmark Tucker SM, Kasaryan A, Karlsson M, Nikolajeff F, Schell H, Outeiro TF, Kahle PJ, Lannfelt L, Ingelsson M, Bergstrom J

Publication type: Article

Publication status: Published

Journal: Amyloid

Year: 2013

Volume: 20

Issue: 4

Pages: 233-244

Online publication date: 20/09/2013

ISSN (print): 1350-6129

ISSN (electronic): 1744-2818

Publisher: Taylor & Francis

URL: https://doi.org/10.3109/13506129.2013.835726

DOI: 10.3109/13506129.2013.835726

PubMed id: 24053224


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