Identification of disulfide cross-linked tau dimer responsible for tau propagation

Dohee Kim, Sungsu Lim, Md Mamunul Haque, Nayeon Ryoo, Hyun Seok Hong, Hyewhon Rhim, Dong Eun Lee, Young Tae Chang, Jun Seok Lee, Eunji Cheong, Dong Jin Kim, Yun Kyung Kim

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number15231
JournalScientific reports
Volume5
DOIs
Publication statusPublished - 2015 Oct 15

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Disulfides
Pathology
Prions
Neurons
Transgenic Mice
Seeds
Mutation
Brain

All Science Journal Classification (ASJC) codes

  • General

Cite this

Kim, D., Lim, S., Haque, M. M., Ryoo, N., Hong, H. S., Rhim, H., ... Kim, Y. K. (2015). Identification of disulfide cross-linked tau dimer responsible for tau propagation. Scientific reports, 5, [15231]. https://doi.org/10.1038/srep15231
Kim, Dohee ; Lim, Sungsu ; Haque, Md Mamunul ; Ryoo, Nayeon ; Hong, Hyun Seok ; Rhim, Hyewhon ; Lee, Dong Eun ; Chang, Young Tae ; Lee, Jun Seok ; Cheong, Eunji ; Kim, Dong Jin ; Kim, Yun Kyung. / Identification of disulfide cross-linked tau dimer responsible for tau propagation. In: Scientific reports. 2015 ; Vol. 5.
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Kim, D, Lim, S, Haque, MM, Ryoo, N, Hong, HS, Rhim, H, Lee, DE, Chang, YT, Lee, JS, Cheong, E, Kim, DJ & Kim, YK 2015, 'Identification of disulfide cross-linked tau dimer responsible for tau propagation', Scientific reports, vol. 5, 15231. https://doi.org/10.1038/srep15231

Identification of disulfide cross-linked tau dimer responsible for tau propagation. / Kim, Dohee; Lim, Sungsu; Haque, Md Mamunul; Ryoo, Nayeon; Hong, Hyun Seok; Rhim, Hyewhon; Lee, Dong Eun; Chang, Young Tae; Lee, Jun Seok; Cheong, Eunji; Kim, Dong Jin; Kim, Yun Kyung.

In: Scientific reports, Vol. 5, 15231, 15.10.2015.

Research output: Contribution to journalArticle

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AU - Lee, Dong Eun

AU - Chang, Young Tae

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AU - Kim, Dong Jin

AU - Kim, Yun Kyung

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