Identification of disulfide cross-linked tau dimer responsible for tau propagation
SCIE
SCOPUS
- Title
- Identification of disulfide cross-linked tau dimer responsible for tau propagation
- Authors
- 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
- Date Issued
- 2015-10
- Publisher
- NATURE PUBLISHING GROUP
- 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.
- Keywords
- NEUROFIBRILLARY TANGLES; ALZHEIMERS-DISEASE; ENDOGENOUS TAU; SYNTHETIC TAU; MOUSE-BRAIN; PATHOLOGY; TRANSMISSION; AGGREGATION; TAUOPATHY; MODEL
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/50377
- DOI
- 10.1038/srep15231
- ISSN
- 2045-2322
- Article Type
- Article
- Citation
- SCIENTIFIC REPORTS, vol. 5, 2015-10
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