Antibodies against alpha-synuclein reduce oligomerization in living cells
2011 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 6, no 10, e27230- p.Article in journal (Refereed) Published
Recent research implicates soluble aggregated forms of α-synuclein as neurotoxic species with a central role in the pathogenesis of Parkinson’s disease and related disorders. The pathway by which α-synuclein aggregates is believed to follow a step-wise pattern, in which dimers and smaller oligomers are initially formed. Here, we used H4 neuroglioma cells expressing α-synuclein fused to hemi:GFP to study the effects of α-synuclein monoclonal antibodies on the early stages of aggregation, as quantified by Bimolecular Fluorescence Complementation assay. Widefield and confocal microscopy revealed that cells treated for 48 h with monoclonal antibodies internalized antibodies to various degrees. Oligomer-selective and C-terminal specific α-synuclein antibodies reduced the extent of α-synuclein dimerization/oligomerization, as indicated by decreased GFP fluorescence signal. Furthermore, ELISA measurements on lysates and conditioned media from antibody treated cells displayed lower α-synuclein levels compared to untreated cells, suggesting increased protein turnover. Taken together, our results propose that extracellular administration of monoclonal antibodies can modify or inhibit early steps in the aggregation process of α-synuclein, thus providing further support for passive immunization against diseases with α-synuclein pathology.
Place, publisher, year, edition, pages
2011. Vol. 6, no 10, e27230- p.
Alpha-synuclein; Parkinson’s disease; Lewy bodies; Aggregation; Bimolecular Fluorescence Complementation; Monoclonal antibodies; Immunotherapy
Neurosciences Cell and Molecular Biology
Research subject Neuroscience; Geriatrics
IdentifiersURN: urn:nbn:se:uu:diva-160097DOI: 10.1371/journal.pone.0027230ISI: 000296916000059PubMedID: 22073131OAI: oai:DiVA.org:uu-160097DiVA: diva2:450411