Rhodanine-based tau aggregation inhibitors in cell models of tauopathy

  • Bulic B
  • Pickhardt M
  • Khlistunova I
 et al. 
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Abstract

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 Delta K280 mutation ("pro-aggregation mutant"), or the repeat domain with Delta K280 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

Author-supplied keywords

  • Aggregation inhibitors
  • Alzheimer's disease
  • Medicinal chemistry
  • Neurochemistry
  • Tau proteins

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