Off-pathway α-synuclein oligomers seem to alter α-synuclein turnover in a cell model but lack seeding capability in vivo. (December 2013)

• Record Type: Journal Article
• Authors: Fagerqvist, Therese; Näsström, Thomas; Ihse, Elisabet; Lindström, Veronica; Sahlin, Charlotte; Fangmark Tucker, Stina M.; Kasaryan, Alex; Karlsson, Mikael; Nikolajeff, Fredrik; Schell, Heinrich; Outeiro, Tiago F.; Kahle, Philipp J.; Lannfelt, Lars; Ingelsson, Martin; Bergström, Joakim
• Is Part Of: Amyloid. Volume 20:Number 4(2013:Dec.)
• Page Start: 233
• Page End: 244
• Publication Date: 2013-12
• Subjects: Amyloidosis -- Periodicals; 616.3995
• DOI: 10.3109/13506129.2013.835726
• Languages: English
• ISSNs: 1350-6129

Abstract

<abstract> <title>Abstract</title> <p>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 <italic>in vitro</italic> and <italic>in vivo</italic> 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 <italic>in vivo</italic> 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.</p> </abstract>