Diaminothiazoles Modify Tau Phosphorylation and Improve the Tauopathy in Mouse Models
dc.contributor.author | Zhang, Xuemei | |
dc.contributor.author | Hernandez, Israel | |
dc.contributor.author | Rei, Damien | |
dc.contributor.author | Mair, Waltraud | |
dc.contributor.author | Laha, Joydev K. | |
dc.contributor.author | Cornwell, Madison E. | |
dc.contributor.author | Cuny, Gregory D. | |
dc.contributor.author | Tsai, Li-Huei | |
dc.contributor.author | Steen, Judith A. J. | |
dc.contributor.author | Kosik, Kenneth S. | |
dc.date.accessioned | 2020-03-10T17:30:56Z | |
dc.date.available | 2020-03-10T17:30:56Z | |
dc.date.issued | 2013-07 | |
dc.description.abstract | Although Tau accumulation is a feature of several neurodegenerative conditions, treatment options for these conditions are nonexistent. Targeting Tau kinases represents a potential therapeutic approach. Small molecules in the diaminothiazole class are potent Tau kinase inhibitors that target CDK5 and GSK3?. Lead compounds from the series have IC50 values toward CDK5/p25 and GSK3? in the low nanomolar range and no observed toxicity in the therapeutic dose range. Neuronal protective effects and decreased PHF-1 immunoreactivity were observed in two animal models, 3×Tg-AD and CK-p25. Treatment nearly eliminated Sarkosyl-insoluble Tau with the most prominent effect on the phosphorylation at Ser-404. Treatment also induced the recovery of memory in a fear conditioning assay. Given the contribution of both CDK5/p25 and GSK3? to Tau phosphorylation, effective treatment of tauopathies may require dual kinase targeting. | |
dc.identifier.citation | Copyright 2013 Journal of Biological Chemistry. Recommended citation: Zhang, Xuemei, Israel Hernandez, Damien Rei, Waltraud Mair, Joydev K. Laha, Madison E. Cornwell, Gregory D. Cuny, Li-Huei Tsai, Judith AJ Steen, and Kenneth S. Kosik. "Diaminothiazoles modify Tau phosphorylation and improve the tauopathy in mouse models." Journal of Biological Chemistry 288, no. 30 (2013): 22042-22056.doi: 10.1074/jbc.M112.436402. URL: http://www.jbc.org/content/288/30/22042. Reproduced in accordance with the original publisher's licensing terms and with permission from the authors. | |
dc.identifier.uri | https://hdl.handle.net/10657/5934 | |
dc.language.iso | en_US | |
dc.publisher | Journal of BIological Chemistry | |
dc.subject | Alzheimer Disease | |
dc.subject | CDK(Cyclin-dependent kinase) | |
dc.subject | Glycogen Synthase Kinase 3 | |
dc.subject | Neurodegenerative diseases | |
dc.subject | Protein Phosphorylation | |
dc.subject | Kinase Inhibitor | |
dc.subject | Tauopathy | |
dc.title | Diaminothiazoles Modify Tau Phosphorylation and Improve the Tauopathy in Mouse Models | |
dc.type | Article |