N-phenylamine derivatives as aggregation inhibitors in cell models of tauopathy.
Cell models of tauopathy were generated in order to study mechanisms of neurodegeneration involving abnormal changes of tau. They are based on neuroblastoma cell lines (N2a) that inducibly express different forms of the repeat domain of tau (tau(RD)), 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 DeltaK280 and two proline point mutations ("anti-aggregation mutant"). The data indicate that the aggregation of tau(RD) is toxic, and that aggregation and toxicity can be prevented by low molecular weight compounds, notably compounds based on the N-phenylamine core. Thus the cell models are suitable for developing aggregation inhibitor drugs.
Pickhardt
M
M
Max-Planck-Unit for Structural Molecular Biology, c/o DESY, Notkestrasse 85, 22607, Hamburg, Germany.
Biernat
J
J
Khlistunova
I
I
Wang
Y-P
YP
Gazova
Z
Z
Mandelkow
E-M
EM
Mandelkow
E
E
D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009447:Neuroblastoma / Q000473:pathology; D017434:Protein Structure, Tertiary; D024801:Tauopathies / Q000188:drug therapy* / Q000235:genetics*
D000814:Aniline Compounds