title: Identification of disulfide cross-linked tau dimer responsible for tau propagation.
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.
authors.affiliation: 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.
authors.forename: Dohee
authors.initials: D
authors.lastname: Kim
authors.affiliation: Korea Institute of Science and Technology (KIST), Brain Science Institute, Center for neuro-medicine, Seoul 136-791, South Korea.
authors.forename: Sungsu
authors.initials: S
authors.lastname: Lim
authors.affiliation: Korea Institute of Science and Technology (KIST), Brain Science Institute, Center for neuro-medicine, Seoul 136-791, South Korea.|Biological Chemistry, University of Science and Technology (UST), Daejon 305-333, South Korea.
authors.forename: Md Mamunul
authors.initials: MM
authors.lastname: Haque
authors.affiliation: Korea Institute of Science and Technology (KIST), Brain Science Institute, Center for Neuroscience, Seoul 136-791, South Korea.
authors.forename: Nayeon
authors.initials: N
authors.lastname: Ryoo
authors.affiliation: Medifron-DBT Inc., Ansan, 425-839, South Korea.
authors.forename: Hyun Seok
authors.initials: HS
authors.lastname: Hong
authors.affiliation: Korea Institute of Science and Technology (KIST), Brain Science Institute, Center for Neuroscience, Seoul 136-791, South Korea.|Department of Neuroscience, University of Science and Technology (UST), Daejon 305-333, South Korea.
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, South Korea.
authors.forename: Dong-Eun
authors.initials: DE
authors.lastname: Lee
authors.affiliation: 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).
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Korea Institute of Science and Technology (KIST), Molecular Recognition Research Center, Seoul 136-791, South Korea.|Biological Chemistry, University of Science and Technology (UST), Daejon 305-333, South Korea.
authors.forename: Jun-Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, South Korea.
authors.forename: Eunji
authors.initials: E
authors.lastname: Cheong
authors.affiliation: Korea Institute of Science and Technology (KIST), Brain Science Institute, Center for neuro-medicine, Seoul 136-791, South Korea.
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: Korea Institute of Science and Technology (KIST), Brain Science Institute, Center for neuro-medicine, Seoul 136-791, South Korea.|Biological Chemistry, University of Science and Technology (UST), Daejon 305-333, South Korea.
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D016296:Mutagenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051381:Rats; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D004220:Disulfides; D016875:tau Proteins