Inhibition of Tau Aggregation in Cell Models of Tauopathy

Author(s): Inna Khlistunova, Marcus Pickhardt, Jacek Biernat, Yipeng Wang, Eva-Maria Mandelkow, Eckhard Mandelkow.

Journal Name: Current Alzheimer Research

Volume 4 , Issue 5 , 2007

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Abstract:

The pathological aggregation of tau into paired helical filaments is a hallmark of several neurodegenerative diseases, including Alzheimers 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 (tauRD) 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 ΔK280 mutation (“pro-aggregation mutant”), or the repeat domain with additional proline mutations (“anti-aggregation mutant”). The aggregation of tauRD 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.

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

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Article Details

VOLUME: 4
ISSUE: 5
Year: 2007
Page: [544 - 546]
Pages: 3
DOI: 10.2174/156720507783018307
Price: $58

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