Inhibition of Tau Aggregation in Cell Models of Tauopathy

Title: Inhibition of Tau Aggregation in Cell Models of Tauopathy

Volume: 4 Issue: 5

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

Affiliation:

• Max-Planck-Unit for Structural Molecular Biology, c/o DESY, Notkestrasse 85, 22607 Hamburg,Germany.,Germany

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

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.

Cite this article as:

Khlistunova Inna, Pickhardt Marcus, Biernat Jacek, Wang Yipeng, Mandelkow Eva-Maria and Mandelkow Eckhard, Inhibition of Tau Aggregation in Cell Models of Tauopathy, Current Alzheimer Research 2007; 4(5) . https://dx.doi.org/10.2174/156720507783018307