Title

Diaminothiazoles modify Tau phosphorylation and improve the tauopathy in mouse models.

Journal

The Journal of biological chemistry

Volume

288

Issue

None

Pages

22042-56

Date

2013-07-26

Authors

Cornwell ME | Cuny GD | Hernandez I | Kosik KS | Laha JK | Mair W | Rei D | Steen JA | Tsai LH | Zhang X

Small molecules in the diaminothiazole class are potent Tau kinase inhibitors that target CDK5 and GSK3β. Lead compounds from the series have IC50 values toward CDK5/p25 and GSK3β 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.

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