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
Current Alzheimer Research
Title: N-Phenylamine Derivatives as Aggregation Inhibitors in Cell Models of Tauopathy
Volume: 4 Issue: 4
Author(s): M. Pickhardt, J. Biernat, I. Khlistunova, Y.-P. Wang, Z. Gazova, E.-M. Mandelkow and E. Mandelkow
Affiliation:
Keywords: Alzheimer's disease, paired helical filaments, tau, drug screening
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.
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Cite this article as:
Pickhardt M., Biernat J., Khlistunova I., Wang Y.-P., Gazova Z., Mandelkow E.-M. and Mandelkow E., N-Phenylamine Derivatives as Aggregation Inhibitors in Cell Models of Tauopathy, Current Alzheimer Research 2007; 4 (4) . https://dx.doi.org/10.2174/156720507781788765
DOI https://dx.doi.org/10.2174/156720507781788765 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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