Search

Your search keyword '"Takeda-Uchimura, Yoshiko"' showing total 19 results
Start Over Author "Takeda-Uchimura, Yoshiko"
19 results on '"Takeda-Uchimura, Yoshiko"'

5. Deficiency of terminal complement pathway inhibitor promotes neuronal tau pathology and degeneration in mice

Author

Britschgi, Markus, Takeda-Uchimura, Yoshiko, Rockenstein, Edward, Johns, Hudson, Masliah, Eliezer, and Wyss-Coray, Tony

Abstract

Abstract Background The neuronal microtubule-associated protein tau becomes hyperphosphorylated and forms aggregates in tauopathies but the processes leading to this pathological hallmark are not understood. Because tauopathies are accompanied by neuroinflammation and the complement cascade forms a key innate immune pathway, we asked whether the complement system has a role in the development of tau pathology. Findings We tested this hypothesis in two mouse models, which expressed either a central inhibitor of complement or lacked an inhibitor of the terminal complement pathway. Complement receptor-related gene/protein y is the natural inhibitor of the central complement component C3 in rodents. Expressing a soluble variant (sCrry) reduced the number of phospho-tau (AT8 epitope) positive neurons in the brain stem, cerebellum, cortex, and hippocampus of aged P301L mutant tau/sCrry double-transgenic mice compared with tau single-transgenic littermates (JNPL3 line). CD59a is the major inhibitor of formation of the membrane attack complex in mice. Intrahippocampal injection of adeno-associated virus encoding mutant human P301L tau into Cd59a−/− mice resulted in increased numbers of AT8-positive cells compared with wild-type controls. This was accompanied by neuronal and synaptic loss and reduced dendritic integrity. Conclusions Our data in two independent mouse models with genetic changes in key regulators of the complement system support the hypothesis that the terminal pathway has an active role in the development of tau pathology. We propose that inhibition of the terminal pathway may be beneficial in tauopathies.

Published
2012

13. Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins

Author

Ray, Sandip, Britschgi, Markus, Herbert, Charles, Takeda-Uchimura, Yoshiko, Boxer, Adam, Blennow, Kaj, Friedman, Leah F, Galasko, Douglas R, Jutel, Marek, Karydas, Anna, Kaye, Jeffrey A, Leszek, Jerzy, Miller, Bruce L, Minthon, Lennart, Quinn, Joseph F, Rabinovici, Gil D, Robinson, William H, Sabbagh, Marwan N, So, Yuen T, Sparks, D Larry, Tabaton, Massimo, Tinklenberg, Jared, Yesavage, Jerome A, Tibshirani, Robert, and Wyss-Coray, Tony

Abstract

Author(s): Sandip Ray [1, 16]; Markus Britschgi [2, 16]; Charles Herbert [1]; Yoshiko Takeda-Uchimura [2]; Adam Boxer [3]; Kaj Blennow [4]; Leah F Friedman [5]; Douglas R Galasko [6]; Marek [...]

Published
2007
Full Text
View/download PDF

17. P2‐294: Microarray profiling reveals autoantibody reactivities against abnormal amyloid peptide conformations decline with age and in Alzheimer's disease

Author

Britschgi, Markus, primary, Olin, Christopher E., additional, Johns, Hudson, additional, Takeda-Uchimura, Yoshiko, additional, Rufibach, Kaspar, additional, Tomooka, Beren, additional, Robinson, William H., additional, Rajadas, Jayakumar, additional, Clark, Christopher M., additional, Fagan, Anne M., additional, Galasko, Douglas G., additional, Holtzman, David M., additional, Jutel, Marek, additional, Leszek, Jerzy, additional, Li, Gail, additional, Peskind, Elaine R., additional, Quinn, Joseph F., additional, Yesavage, Jerome A., additional, Ghiso, Jorge A., additional, and Wyss-Coray, Tony, additional

Published
2008
Full Text
View/download PDF

19. KSGal6ST Is Essential for the 6-Sulfation of Galactose within Keratan Sulfate in Early Postnatal Brain

Author

Hoshino, Hitomi, Foyez, Tahmina, Ohtake-Niimi, Shiori, Takeda-Uchimura, Yoshiko, Michikawa, Makoto, Kadomatsu, Kenji, and Uchimura, Kenji

Abstract

Keratan sulfate (KS) comprises repeating disaccharides of galactose (Gal) and N-acetylglucosamine (GlcNAc). Residues of Gal and GlcNAc in KS are potentially modified with sulfate at their C-6 positions. The 5D4 monoclonal antibody recognizes KS structures containing Gal and GlcNAc, both 6-sulfated, and has been used most extensively to evaluate KS expression in mammalian brains. We previously showed that GlcNAc6ST1 is an enzyme responsible for the synthesis of the 5D4 epitope in developing brain and in the adult brain, where it is induced after injury. It has been unclear which sulfotransferase is responsible for Gal-6-sulfation within the 5D4 KS epitope in developing brains. We produced mice deficient in KSGal6ST, a Gal-6-sulfotransferase. Western blotting and immunoprecipitation revealed that all 5D4-immunoreactivity to proteins, including phosphacan, were abolished in KSGal6ST-deficient postnatal brains. Likewise, the 5D4 epitope, expressed primarily in the cortical marginal zone and subplate and dorsal thalamus, was eliminated in KSGal6ST-deficient mice. Disaccharide analysis showed the loss of Gal-6-sulfate in KS of the KSGal6ST-deficient brains. Transfection studies revealed that GlcNAc6ST1 and KSGal6ST cooperated in the expression of the 5D4 KS epitope in HeLa cells. These results indicate that KSGal6ST is essential for C-6 sulfation of Gal within KS in early postnatal brains.

Published
2014
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results