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Kinetics and Thermodynamics of Amyloid Fibril Assembly

Ronald Wetzel*

Graduate School of Medicine, University of Tennessee, 1924 Alcoa Highway, Knoxville, Tennessee 37920

Acc. Chem. Res., 2006, 39 (9), pp 671–679

DOI: 10.1021/ar050069h

Publication Date (Web): July 22, 2006

Current address: Department of Structural Biology, University of Pittsburgh School of Medicine, 3501 Fifth Avenue, Pittsburgh, PA 15260.

Ronald Wetzel was born in Hanover, PA, in 1946. He obtained a B.S. in Chemistry from Drexel University in 1969 and a Ph.D. in physical organic chemistry from the University of California, Berkeley, in 1973, after which came postdoctoral training at the Max Planck Institute for Experimental Medicine and at Yale University. He has served as a senior scientist at Genentech and as a senior research fellow at SmithKline Beecham and is now Professor in the Graduate School of Medicine at the University of Tennessee. His main scientific interest for 25 years has been protein misfolding and aggregation.

Abstract

With some exceptions, amyloids appear to be accidental aggregated structures whose formation was not selected for in molecular evolution. Despite this, amyloid fibrils are in many respects surprisingly well-behaved molecules. For example, Huntington's disease-related polyglutamine sequences aggregate via a relatively simple nucleated growth polymerization mechanism. In addition, the Alzheimer's plaque protein Aβ has been shown to undergo reversible amyloid fibril formation to a position of dynamic equilibrium such that reaction thermodynamics can be quantified. Studies of these well-behaved amyloid systems are allowing us to peer more deeply into the process and products of off-pathway misfolding and aggregation.

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