title: α-Synuclein modifies huntingtin aggregation in living cells.
abstract: Several neurodegenerative disorders are characterized by the accumulation of proteinaceous inclusions in the central nervous system. These inclusions are frequently composed of a mixture of aggregation-prone proteins. Here, we used a bimolecular fluorescence complementation assay to study the initial steps of the co-aggregation of huntingtin (Htt) and α-synuclein (α-syn), two aggregation-prone proteins involved in Huntington's disease (HD) and Parkinson's disease (PD), respectively. We found that Htt (exon 1) oligomerized with α-syn and sequestered it in the cytosol. In turn, α-syn increased the number of cells displaying aggregates, decreased the number of aggregates per cell and increased the average size of the aggregates. Our results support the idea that co-aggregation of aggregation-prone proteins can contribute to the histopathology of neurodegenerative disorders.
authors: Cell and Molecular Neuroscience Unit, Instituto de Medicina Molecular, Lisboa, Portugal.
authors: Federico
authors: F
authors: Herrera
authors: Tiago Fleming
authors: TF
authors: Outeiro
mesh_terms: D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D005091:Exons; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000378:metabolism / Q000473:pathology; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D051844:alpha-Synuclein