Unraveling the amyloid fibril with polyphenols

2006 Pilot Project Read More

Investigators

Principal Investigator: Jin-Moo Lee, MD, PhD (WUSTL Neurology)
Co-investigators: Carl Frieden, PhD (WUSTL Biochemistry), John Heuser, MD (WUSTL Cell Biology & Physiology), Rohit Pappu, PhD (WUSTL Biomedical Engineering), David Wozniak, PhD (WUSTL Psychiatry)

Description

Polyphenols are natural substances found in vegetables, fruits, roots, flowers, tea, and wine. These micronutrients have antioxidant properties and may play a role in disease prevention. This project will discover whether specific polyphenols can reverse the pathological aggregation of amyloid protein and amyloid plaques of Alzheimer’s Disease. This project brings together accomplished investigators from five departments, with a remarkable range of experimental techniques from high resolution atomic force microscopy to mouse behavior.

Funded Grants

“Untangling Amyloid Plaques with Proteases” NIH/NINDS R01 NS067905-01   (PI, Lee)
The aim of this project is to investigate the Aβ-degrading and amyloid fibril-degrading activity of MMP-9 in an animal model of Alzheimer’s disease to determine its role in plaque pathogenesis.

Publications

Zhang R, Hu X, Khant H, Ludtke SJ, Chiu W, Schmid MF, Frieden C, Lee JM. Inter-protofilament interactions between Alzheimer’s Abeta1-42 peptides in amyloid fibrils revealed by cryoEM. PNAS (2009).

Hu X, Crick SL, Bu G, Frieden C, Pappu RV, Lee JM. Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide. PNAS (2009).

Yan P., Bero A., Cirrito J.R., Xiao Q., Hu X., Wang Y., Gonzales E., Holtzman D.M., Lee J.-M., Characterizing the appearance and growth of amyloid plaques in APP/PS1 mice. J Neurosci (2009).

Hu S., Yan P., Maslov K., Lee J.-M., Wang L.V.  Intravital imaging of amyloid plaques in a transgenic mouse model using optical-resolution photacoustic microscopy. Optic Letters (2009).


Updated January 2014

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