Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep15231
Title: Identification of disulfide cross-linked tau dimer responsible for tau propagation
Authors: Kim, D
Lim, S
Haque, M.M
Ryoo, N
Hong, H.S
Rhim, H
Lee, D.-E
Chang, Y.-T 
Lee, J.-S
Cheong, E
Kim, D.J
Kim, Y.K
Keywords: disulfide
tau protein
animal
brain
cell culture
chemistry
cytology
dimerization
fluorescence microscopy
genetics
HEK293 cell line
human
metabolism
mouse
mutagenesis
nerve cell
pathology
rat
transgenic mouse
transmission electron microscopy
Animals
Brain
Cells, Cultured
Dimerization
Disulfides
HEK293 Cells
Humans
Mice
Mice, Transgenic
Microscopy, Electron, Transmission
Microscopy, Fluorescence
Mutagenesis
Neurons
Rats
tau Proteins
Issue Date: 2015
Publisher: Nature Publishing Group
Citation: Kim, D, Lim, S, Haque, M.M, Ryoo, N, Hong, H.S, Rhim, H, Lee, D.-E, Chang, Y.-T, Lee, J.-S, Cheong, E, Kim, D.J, Kim, Y.K (2015). Identification of disulfide cross-linked tau dimer responsible for tau propagation. Scientific Reports 5 : 15231. ScholarBank@NUS Repository. https://doi.org/10.1038/srep15231
Rights: Attribution 4.0 International
Abstract: Recent evidence suggests that tau aggregates are not only neurotoxic, but also propagate in neurons acting as a seed for native tau aggregation. Prion-like tau transmission is now considered as an important pathogenic mechanism driving the progression of tau pathology in the brain. However, prion-like tau species have not been clearly characterized. To identify infectious tau conformers, here we prepared diverse tau aggregates and evaluated the effect on inducing intracellular tau-aggregation. Among tested, tau dimer containing P301L-mutation is identified as the most infectious form to induce tau pathology. Biochemical analysis reveals that P301L-tau dimer is covalently cross-linked with a disulfide bond. The relatively small and covalently cross-linked tau dimer induced tau pathology efficiently in primary neurons and also in tau-transgenic mice. So far, the importance of tau disulfide cross-linking has been overlooked in the study of tau pathology. Here our results suggested that tau disulfide cross-linking might play critical role in tau propagation by producing structurally stable and small tau conformers.
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/180425
ISSN: 2045-2322
DOI: 10.1038/srep15231
Rights: Attribution 4.0 International
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