The molecular chaperone Brichos breaks the catalytic cycle that generates toxic Aβ oligomers
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چکیده
where two particular combinations of the rate constants for primary nucleation (kn), elongation (k+), and fibril-catalysed secondary nucleation (k2) define much of the macroscopic behaviour; these parameters are related to the rate of formation of new aggregates through primary pathways λ = �2k+knm(0)c and through secondary pathways κ = �2k+k2m(0)2. Indeed, Eq. 1 depends on the rate constants through these two parameters, λ and κ, alone since B± = (k∞ ± k�∞)/(2κ), C± = ±λ2/(2κ2), k∞ = �2κ2 [n2(n2 + 1)] + 2λ/nc ⁄ and k�∞ = �k∞ 2 − 4C+C−κ. The initial concentration of soluble monomers is denoted m(0) and the exponents describing the dependencies of the primary and secondary pathways on the monomer concentration are given as nc and n2 respectively.
منابع مشابه
Aggregation of the amyloid-β peptide (Aβ) into toxic oligomers and amyloid fibrils is linked to the development of Alzheimer’s disease (AD). Mutations of the BRICHOS chaperone domain are associated with amyloid disease and recent in vitro data show that BRICHOS
659 ABSTRACT Aggregation of the amyloid-β peptide (Aβ) into toxic oligomers and amyloid fibrils is linked to the development of Alzheimer’s disease (AD). Mutations of the BRICHOS chaperone domain are associated with amyloid disease and recent in vitro data show that BRICHOS efficiently delays Aβ42 oligomerization and fibril formation. We have generated transgenic Drosophila melanogaster flies t...
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