| Summary: | 碩士 === 國立陽明大學 === 放射醫學科學研究所 === 90 === 英文摘要
Alzheimer’s disease (AD) is one of the leading causes of death in the elderly of the developed world. This widespread progressive neurodegeneration is characterized by the presence of proteinaceous deposits in the brain described as amyloid on the basis of tinctorial properties. Substantial evidence indicates that aggregation of β-amyloid (Aβ) peptides (Aβ1-40 and Aβ1-42) resulting neuronal toxicity probably play a causative role in the etiology of AD.
Past studies of the kinetics of Aβpolymerization, utilizing turbidity, sedimentation and dye binding, could only provide information on the appearance of high molecular weight aggregates. Rate constants could not be determined by these approaches. In contrast, surface plasmon resonance(SPR) biosensor can be used to monitor binding events in real time without labeling, making them convenient for studying early-stage Aβ polymerization. Besides, SPR technology is capable of high sensitivity, therefore, it can be conducted to collect kinetic data for rapid binding events of small molecular weight peptide on the seconds time scale.
We have studied Aβ1-42 aggregation at different concentrations from 100 to 600nM, the results show that the association rate constant (ka) is strongly dependent upon the Aβ concentration, but the dissociation rate constant (kd) influenced by buffer has no salient change.
The experimental results of Aβ protein variants Aβ1-42 and Aβ1-40 show that the C-terminus of Aβ affects the rate of amyloid aggregation. The Aβ1-42 protein is capable of higher tendency to produce self-assembly and to generate new binding site by conformation transition.
Using nicotine and extract of Gingko biloba, EGb761, as inhibitors, it has been shown that both of them can retard Aβ1-42 polymerization and promote dissociation in the association and dissociation phase.
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