title: Development of tau aggregation inhibitors for Alzheimer's disease.
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.
authors.affiliation: Max-Planck-Institute for Molecular Physiology, Dortmund, Germany. bruno.bulic@mpi-dortmund.mpg.de
authors.forename: Bruno
authors.initials: B
authors.lastname: Bulic
authors.forename: Marcus
authors.initials: M
authors.lastname: Pickhardt
authors.forename: Boris
authors.initials: B
authors.lastname: Schmidt
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Mandelkow
authors.forename: Herbert
authors.initials: H
authors.lastname: Waldmann
authors.forename: Eckhard
authors.initials: E
authors.lastname: Mandelkow
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology; D000682:Amyloid / Q000037:antagonists & inhibitors; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors; D052160:Benzothiazoles; D016208:Databases, Factual; D006801:Humans; D024801:Tauopathies / Q000188:drug therapy; D013844:Thiazoles / Q000378:metabolism; D016875:tau Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D013844:Thiazoles; D016875:tau Proteins; C009462:thioflavin T