Inhibition of tau aggregation in cell models of tauopathy.
The pathological aggregation of tau into paired helical filaments is a hallmark of several neurodegenerative diseases, including Alzheimer's disease. We have generated cell models of tau aggregation in order to study mechanisms involving abnormal changes of tau. In the cell models the repeat domain of tau (tau(RD)) and some of its variants are expressed in a regulated fashion, e.g. the 4-repeat domain of tau with the wild-type sequence, the repeat domain with the deltaK280 mutation ("pro-aggregation mutant"), or the repeat domain with additional proline mutations ("anti-aggregation mutant"). The aggregation of tau(RD) is toxic to the cells, but aggregation and toxicity can be prevented by low molecular weight compounds identified by a screen for inhibitors. Thus the cell models are suitable for developing aggregation inhibitor drugs and testing their cellular roles.
Khlistunova
Inna
I
Max-Planck-Unit for Structural Molecular Biology, Notkestrasse 85, 22607 Hamburg, Germany.
Pickhardt
Marcus
M
Biernat
Jacek
J
Wang
Yipeng
Y
Mandelkow
Eva-Maria
EM
Mandelkow
Eckhard
E
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008954:Models, Biological; D009154:Mutation / Q000502:physiology; D024801:Tauopathies / Q000378:metabolism*; D014162:Transfection; D016875:tau Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D016875:tau Proteins