PuSH - Publication Server of Helmholtz Zentrum München

Paquet, D.* ; Bhat, R.* ; Sydow, A.* ; Mandelkow, E.-M.* ; Berg, S.* ; Hellberg, S.* ; Fälting, J.* ; Distel, M. ; Köster, R.W. ; Schmid, B.* ; Haass, C.*

A zebrafish model of tauopathy allows in vivo imaging of neuronal cell death and drug evaluation.

J. Clin. Invest. 119, 1382-1395 (2009)
Publ. Version/Full Text Volltext DOI PMC
Free by publisher
Open Access Green as soon as Postprint is submitted to ZB.
Our aging society is confronted with a dramatic increase of patients suffering from tauopathies, which include Alzheimer disease and certain frontotemporal dementias. These disorders are characterized by typical neuropathological lesions including hyperphosphorylation and subsequent aggregation of TAU protein and neuronal cell death. Currently, no mechanism-based cures are available. We generated fluorescently labeled TAU transgenic zebrafish, which rapidly recapitulated key pathological features of tauopathies, including phosphorylation and conformational changes of human TAU protein, tangle formation, neuronal and behavioral disturbances, and cell death. Due to their optical transparency and small size, zebrafish larvae are well suited for both in vivo imaging and drug development. TAU-induced neuronal cell death was imaged by time-lapse microscopy in vivo. Furthermore, we used this zebrafish model to identify compounds targeting the TAU kinase glycogen synthase kinase 3(3 (GSK3 beta). We identified a newly developed highly active GSK3 beta inhibitor, AR-534, by rational drug design. AR-534 reduced TAU phosphorylation in TAU transgenic zebrafish. This transgenic zebrafish model may become a valuable tool for further studies of the neuropathology of dementia.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords paired helical filaments; glycogen-synthase kinase-3; protein-tau tau; alzheimers-disease; transgenic zebrafish; neurodegenerative diseases; danio-rerio; phosphorylation; degeneration; expression
ISSN (print) / ISBN 0021-9738
e-ISSN 1558-8238
Journal Journal of Clinical Investigation
Quellenangaben Volume: 119, Issue: 5, Pages: 1382-1395 Article Number: , Supplement: ,
Publisher American Society of Clinical Investigation
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)