Bergstrom J

Fagerqvist T

Fangmark Tucker SM

Ihse E

Ingelsson M

Kahle PJ

Karlsson M

Kasaryan A

Lannfelt L

Lindstrom V

Nasstrom T

Nikolajeff F

Outeiro TF

Sahlin C

Schell H

Aggregated α-synuclein is the major component of Lewy bodies, protein inclusions observed in the brain in neurodegenerative disorders such as Parkinson\u27s 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. \ua9 2013 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted

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

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

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