Journal article
Targeting metals rescues the phenotype in an animal model of tauopathy
A Sedjahtera, L Gunawan, L Bray, LW Hung, J Parsons, N Okamura, VL Villemagne, K Yanai, XM Liu, J Chan, AI Bush, DI Finkelstein, KJ Barnham, RA Cherny, PA Adlard
Metallomics | ROYAL SOC CHEMISTRY | Published : 2018
DOI: 10.1039/c8mt00153g
Abstract
Tauopathies are characterized by the pathological accumulation of the microtubule associated protein tau within the brain. We demonstrate here that a copper/zinc chaperone (PBT2, Prana Biotechnology) has rapid and profound effects in the rTg(tau P301L )4510 mouse model of tauopathy. This was evidenced by significantly improved cognition, a preservation of neurons, a decrease in tau aggregates and a decrease in other forms of “pathological” tau (including phosphorylated tau and sarkosyl-insoluble tau). Our data demonstrate that one of the primary mechanisms of action of PBT2 in this model may be driven by an interaction on the pathways responsible for the dephosphorylation of tau. Specificall..
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Awarded by Australian Research Council
Funding Acknowledgements
PAA, DIF, AIB and RAC are variously supported by the National Health and Medical Research Council. PAA is also supported by the Australian Research Council. The Florey Institute of Neuroscience and Mental Health acknowledge the strong support from the Victorian Government and in particular the funding from the Operational Infrastructure Support Grant. We also acknowledge the assistance of Dr Penny Huggins and Dr Silas Bond for their ongoing assistance with chemistry, the provision of compound and the refinement of in vitro screening assays.