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Osmolytes affect the kinetics of Abeta (1‐42) aggregation
Author(s) -
Heldt Caryn L,
Sorci Mirco,
Belfort Georges
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.851.8
Subject(s) - oligomer , osmolyte , circular dichroism , chemistry , kinetics , biophysics , peptide , biochemistry , organic chemistry , biology , physics , quantum mechanics
The formation of plaques in the brains of Alzheimer's patients has long been thought to be the disease causing agent. Yet, recent data has shown that small oligomers of Abeta that form prior to plaque formation may actually be the toxic disease causing agent. But little is known about these small oligomer species. We have examined the formation of the small oligomers created from Abeta (1‐42) to better understand the formation of these suspected toxic species. Using circular dichroism, the transition of the peptide from a random configuration to an ordered beta sheet oligomer was observed and the kinetic rates were examined to determine how the addition of different osmolytes affected the oligomer formation. With the use of small‐angle scattering, we have examined the rate of change of the size of these small oligomer species under aggregating conditions. By changing the concentration of osmolytes in the solution, we were able to increase and decrease the kinetic rates of the aggregation process and learn more about the chemical environment that causes the transition of Abeta (1‐42) from random peptide to structured oligomer. This information is important to understand the molecular basis of Alzheimer's disease and brings us closer to creating a drug that can slow or stop the progression of this disease. This work was funded by the U.S. Department of Energy, DOE (DE‐FG02‐07ER46429).