Modeling Prion-Like Processing of Tau Protein in Alzheimer's Disease for Pharmaceutical Development

Autor: Wischik, Claude M, Schelter, Björn O, Wischik, Damon J, Storey, John MD, Harrington, Charles R
Přispěvatelé: Storey, John MD [0000-0002-5261-5467], Harrington, Charles R [0000-0003-2250-3920], Apollo - University of Cambridge Repository
Rok vydání: 2018
Předmět:
Popis: Following our discovery of a fragment from the repeat domain of tau protein as a structural constituent of the PHF-core in Alzheimer's disease (AD), we developed an assay that captured several key features of the aggregation process. Tau-tau binding through the core tau fragment could be blocked by the same diaminophenothiazines found to dissolve proteolytically stable PHFs isolated from AD brain. We found that the PHF-core tau fragment is inherently capable of auto-catalytic self-propagation in vitro, or "prion-like processing", that has now been demonstrated for several neurodegenerative disorders. Here we review the findings that led to the first clinical trials to test tau aggregation inhibitor therapy in AD as a way to block this cascade. Although further trials are still needed, the results to date suggest that a treatment targeting the prion-like processing of tau protein may have a role in both prevention and treatment of AD.
Databáze: OpenAIRE