title: Monomer Dynamics of Alzheimer Peptides and Kinetic Control of Early Aggregation in Alzheimer's Disease.
abstract: The rate of reconfiguration-or intramolecular diffusion-of monomeric Alzheimer (Aβ) peptides is measured and, under conditions that aggregation is more likely, peptide diffusion slows down significantly, which allows bimolecular associations to be initiated. By using the method of Trp-Cys contact quenching, the rate of reconfiguration is observed to be about five times faster for Aβ40, which aggregates slowly, than that for Aβ42, which aggregates quickly. Furthermore, the rate of reconfiguration for Aβ42speeds up at higher pH, which slows aggregation, and in the presence of the aggregation inhibitor curcumin. The measured reconfiguration rates are able to predict the early aggregation behavior of the Aβ peptide and provide a kinetic basis for why Aβ42is more prone to aggregation than Aβ40, despite a difference of only two amino acids.
authors.affiliation: Department of Physics and Astronomy, Michigan State University, 567 Wilson Rd. Rm 4227, East Lansing, MI, 48824, USA.
authors.forename: Srabasti
authors.initials: S
authors.lastname: Acharya
authors.affiliation: Department of Physics and Astronomy, Michigan State University, 567 Wilson Rd. Rm 4227, East Lansing, MI, 48824, USA.
authors.forename: Kinshuk R
authors.initials: KR
authors.lastname: Srivastava
authors.affiliation: Department of Physics and Astronomy, Michigan State University, 567 Wilson Rd. Rm 4227, East Lansing, MI, 48824, USA.
authors.forename: Sureshbabu
authors.initials: S
authors.lastname: Nagarajan
authors.affiliation: Department of Physics and Astronomy, Michigan State University, 567 Wilson Rd. Rm 4227, East Lansing, MI, 48824, USA.|Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Lapidus
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D003474:Curcumin / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D066329:Protein Aggregates / Q000187:drug effects; D013816:Thermodynamics
chemical_list: D016229:Amyloid beta-Peptides; D066329:Protein Aggregates; D003474:Curcumin
keywords: Alzheimer's disease; aggregation; inhibitors; kinetics; peptides