P3–302: Aggregational properties of wild–type and mutated tau proteinстатья из журнала
Аннотация: Mutations in the tau gene cause frontotemporal dementia with parkinsonism (FTDP–17). Some of the tau mutations are intronic and influence tau exon 10 splicing, leading to a shift in the ratio of tau with four (4R tau) and three (3R tau) microtubule binding repeats. However, a majority of tau mutations are located in exons and have instead been proposed to increase tau aggregation. The aggregational properties of the different tau isoforms have only been partly elucidated and it also remains unclear whether the presence of mutated tau may induce aggregation of wild–type tau isoforms. To investigate different aspects of wild–type and mutated tau protein aggregation in vitro. A tau aggregation assay, based on the fluorescent dye thioflavine T and with heparin as inducer, was designed. Single and mixed preparations of wild type tau isoforms as well as 4R tau versions of the three common tau mutations P301LV337M and R406W were studied. In accordance with previous studies, the tau mutants aggregated faster and to a greater extent than wild–type tau. Tau R406W was the most rapidly aggregating mutant, followed by P301L and V337M, respectively. Moreover, mixed samples with 75% 4R tau or 75% 3R tau had a slightly higher propensity to aggregate compared to samples with equal representation of 4R tau and 3R tau. Finally, cryo transmission electron microscopy demonstrated that fibrils formed by the various tau mutants were much more numerous, but had a roughly similar morphological appearance as fibrils formed by wild–type tau. Our results confirm previous findings of tau mutants aggregating faster and to a greater extent than wild–type tau. Moreover, preliminary evidence suggest that preparations with a inbalance of 4R tau and 3R tau isoforms are particularly prone to aggregate, which may reflect a pathogenic mechanism for tauopathies with a shift in tau exon 10 splicing.
Год издания: 2006
Авторы: Cecilia Fägerblad, Johan Fredriksson, Lena Skoglund, Joakim Bergström, Lars Lannfelt, Martin Ingelsson
Издательство: Wiley
Источник: Alzheimer s & Dementia
Ключевые слова: Alzheimer's disease research and treatments, Prion Diseases and Protein Misfolding, Biotin and Related Studies
Открытый доступ: bronze
Том: 2
Выпуск: 3S_Part_15