antibodies against alpha-synuclein reduce oligomerization in living cellsα-突触核蛋白抗体减少低聚在活细胞.pdf

Antibodies against Alpha-Synuclein Reduce Oligomerization in Living Cells ¨ ¨ 1 2 1 ¨ 4 Thomas Nasstrom , Susana Gonc¸alves , Charlotte Sahlin , Eva Nordstrom , Valentina Screpanti 4 1 ¨ 1 2,3,5 1 Sundquist , Lars Lannfelt , Joakim Bergstrom , Tiago F. Outeiro , Martin Ingelsson * 1 Rudbeck Laboratory, Department of Public Health/Geriatrics, Uppsala University, Uppsala, Sweden, 2 Cell and Molecular Neuroscience Unit, Instituto de Medicina Molecular, Lisboa, Portugal, 3 Instituto de Fisiologia, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal, 4 BioArctic Neuroscience AB, Stockholm, Sweden, ¨ ¨ ¨ 5 Department of NeuroDegeneration and Restaurative Research, Universitatsmedizin Gottingen, Gottingen, Germany Abstract Recent research implicates soluble aggregated forms of a-synuclein as neurotoxic species with a central role in the pathogenesis of Parkinson’s disease and related disorders. The pathway by which a-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 a-synuclein fused to hemi:GFP constructs to study the effects of a-synuclein monoclonal antibodies on the early stages of aggregation, as quantified by Bimolecular Fluorescence Complementation assay. Widefield and confocal microscopy revealed that ce