N-Phenylamine Derivatives as Aggregation Inhibitors in Cell Models of Tauopathy

Author(s): M. Pickhardt , J. Biernat , I. Khlistunova , Y.-P. Wang , Z. Gazova , E.-M. Mandelkow , E. Mandelkow .

Journal Name: Current Alzheimer Research

Volume 4 , Issue 4 , 2007

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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 (tauRD), e.g. the 4-repeat domain of tau with the wild-type sequence, the repeat domain with the ΔK280 mutation (“pro-aggregation mutant”), or the repeat domain with ΔK280 and two proline point mutations (“anti-aggregation mutant”). The data indicate that the aggregation of tauRD 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.

Keywords: Alzheimer's disease, paired helical filaments, tau, drug screening

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Article Details

VOLUME: 4
ISSUE: 4
Year: 2007
Page: [397 - 402]
Pages: 6
DOI: 10.2174/156720507781788765
Price: $58

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