Send to

Choose Destination
Sci Rep. 2015 Oct 15;5:15231. doi: 10.1038/srep15231.

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

Author information

Korea Institute of Science and Technology (KIST), Brain Science Institute, Center for neuro-medicine, Seoul 136-791, South Korea.
Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, South Korea.
Biological Chemistry, University of Science and Technology (UST), Daejon 305-333, South Korea.
Korea Institute of Science and Technology (KIST), Brain Science Institute, Center for Neuroscience, Seoul 136-791, South Korea.
Medifron-DBT Inc., Ansan, 425-839, South Korea.
Department of Neuroscience, University of Science and Technology (UST), Daejon 305-333, South Korea.
Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, South Korea.
Department of Chemistry &Med Chem Program, National University of Singapore, 3 Science Drive 2, 117543 Singapore (Singapore).
Singapore BioImaging Consortium, Agency for Science, Technology and Research, 11 Biopolis Way, 138667 Singapore (Singapore).
Korea Institute of Science and Technology (KIST), Molecular Recognition Research Center, Seoul 136-791, South Korea.


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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center