Development of tau aggregation inhibitors for Alzheimer's disease.

Max-Planck-Institute for Molecular Physiology, Dortmund, Germany.
Angewandte Chemie International Edition (Impact Factor: 11.34). 03/2009; 48(10):1740-52. DOI: 10.1002/anie.200802621
Source: PubMed

ABSTRACT A variety of human diseases are suspected to be directly linked to protein misfolding. Highly organized protein aggregates, called amyloid fibrils, and aggregation intermediates are observed; these are considered to be mediators of cellular toxicity and thus attract a great deal of attention from investigators. Neurodegenerative pathologies such as Alzheimer's disease account for a major part of these protein misfolding diseases. The last decade has witnessed a renaissance of interest in inhibitors of tau aggregation as potential disease-modifying drugs for Alzheimer's disease and other "tauopathies". The recent report of a phase II clinical trial with the tau aggregation inhibitor MTC could hold promise for the validation of the concept. This Review summarizes the available data concerning small-molecule inhibitors of tau aggregation from a medicinal chemistry point of view.

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