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7064574 
Journal Article 
The Diarylheptanoid (+)-aR,11S-Myricanol and Two Flavones from Bayberry (Myrica cerifera) Destabilize the Microtubule-Associated Protein Tau 
Jones, , JR; Johnson, AG; Weeber, E; Eckman, CB; Baker, BJ; Dickey, CA; Lebar, MD; Jinwal, UK; Abisambra, JF; Koren, J III; Blair, L; O'Leary, JC; Davey, Z; Trotter, J; , 
2011 
Yes 
Journal of Natural Products
ISSN: 0163-3864
EISSN: 1520-6025 
AMER CHEMICAL SOC 
WASHINGTON 
74 
1 
38-44 
English 
21141876 
WOS:000286577800008 
Target-based drug discovery for Alzheimer's disease (AD) centered on modulation of the amyloid beta peptide has met with limited success. Therefore, recent efforts have focused on targeting the microtubule-associated protein tau. Tau pathologically accumulates in more than 15 neurodegenerative diseases and is most closely linked with postsymptomatic progression in AD. We endeavored to identify compounds that decrease tau stability rather than prevent its aggregation. An extract from Myrica cerifera (bayberry/southern wax myrtle) potently reduced both endogenous and overexpressed tau protein levels in cells and murine brain slices. The bayberry flavonoids myricetin and myricitrin were confirmed to contribute to this potency, but a diarylheptanoid, myricanol, was the most effective anti-tau component in the extract, with potency approaching the best targeted lead therapies. (+)-aR,11S-Myricanol, isolated from M. cerifera and reported here for the first time as the naturally occurring aglycone, was significantly more potent than commercially available (+/-)-myricanol. Myricanol may represent a novel scaffold for drug development efforts targeting tau turnover in AD.