The development of therapeutics for Alzheimer's disease (AD) is of critical importance to the United States due to the enormous expected growth of the elderly population within the next 2 decades. While much of the effort toward pharmacological intervention in this disease has been directed toward amyloid, recent evidence has emerged suggesting that the other central pathological component, tau, may be a necessary therapeutic target, particularly in patients who already have disease symptoms. Here, we have developed a unique methodology that allows for the rapid analysis of tau levels, providing an efficient way to monitor the efficacy of compounds directed toward intracellular targets such as tau. By using this technique we propose to 1) identify new compounds that alter tau and begin to define their mechanism of action, and 2) better characterize drugs that upregulate molecular chaperone expression a protective cascade that has been implicated in the removal of pathological tau species and which has also been implicated in other diseases linked to abnormal protein accumulation. Those compounds with the greatest promise based on in vitro analyses will then be used in animal models for tauopathy that are exclusive to the Mayo Clinic. ? ?
| Jones, Jeffrey R; Lebar, Matthew D; Jinwal, Umesh K et al. (2011) The diarylheptanoid (+)-aR,11S-myricanol and two flavones from bayberry (Myrica cerifera) destabilize the microtubule-associated protein tau. J Nat Prod 74:38-44 |
