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

Nikolajeff, Fredrik (author): Uppsala universitet,Tillämpad materialvetenskap

Schell, Heinrich (author): Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, Tübingen

Outeiro, Tiago. F (author): Cell and Molecular Neuroscience Unit, Instituto de Medicina Molecular, Lisboa. Instituto de Fisiologia, Faculdade de Medicina da Universidade de Lisboa, Lisboa. Department of NeuroDegeneration and Restaurative Research, Universitätsmedizin Göttingen, Göttingen

Kahle, Philipp J (author): Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, Tübingen

(creator_code:org_t)

2013-09-20
2013
English.
In: Amyloid. - : Informa UK Limited. - 1350-6129 .- 1744-2818. ; 20:4, s. 233-244

Related links:: https://urn.kb.se/re...; show more...; https://doi.org/10.3...; show less...

Abstract Subject headings

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.

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)

By the author/editor: Fagerqvist, Ther ...; Näsström, Thomas; Ihse, Elisabet; Lindström, Veron ...; Sahlin, Charlott ...; Fangmark Tucker, ...; show more...; Kasaryan, Alex; Karlsson, Mikael; Nikolajeff, Fred ...; Schell, Heinrich; Outeiro, Tiago. ...; Kahle, Philipp J; Lannfelt, Lars; Ingelsson, Marti ...; Bergström, Joaki ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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