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The Interaction between Copper Ions and Different Aggregated Forms of Aβ in Alzheimer’s Disease

Author: FangChuanLin
Tutor: MaYuan
School: Tsinghua University
Course: Chemistry
Keywords: Alzheimer's disease amyloid beta peptides Oligomers Fiber body Copper ions
CLC: R749.16
Type: Master's thesis
Year: 2010
Downloads: 204
Quote: 0
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Abstract


Alzheimer's disease (Alzheimer's disease, AD) is a neurodegenerative disease. beta amyloid (Aβ) peptides pathological accumulation and oxidative stress generation are iconic signal of AD. Aβ is a combination with copper ions and the electrochemically active metal protein, copper ions may restore it further the O 2 into H 2 O 2 , but it has been reported that Aβ can inhibit the generation of oxidative stress. In addition, studies have found that the interaction of Aβ with copper, copper-induced Aβ further aggregation. This thesis angle from oxidative stress by three different aggregation forms of the study of the interaction of Aβ with copper, indicating three different Aβ aggregates exhibit different behavior in the interaction process with copper. In addition, the toxicity of Aβ three different aggregates. In this thesis, synthesis of Aβ and prepared three different aggregates of Aβ, thioflavin T (ThT) fluorescence assay gathered state and molecular exclusion chromatography and transmission electron microscopy were monomers, oligomers, fiber body of quantitative and qualitative characterization. Then used the TCA ethylphosphonic -5,5 '- dithio / bis (2 - nitrobenzoic acid) (TCEP-DTNB) detection of Aβ with copper during the interaction of the H 2 the O 2 (H 2 DCF-DA) and 2 ', 7'-dichlorofluorescein fluorescence acetyl acetate experiment further confirmed by three different Aβ aggregates copper interaction in generating H 2 O 2 aspects of exhibit different behavior. Copper ion concentration gradient used in the experiment within the range (0.2-1.4μM), the monomer has always demonstrated inhibition of H 2 O 2 generated role; oligomers with fiber body with the changes in the concentration of copper ions and the role of different when the system copper ion concentration is less than 0.8 m, the oligomers and fiber exhibit promote the H 2 O 2 role; when the copper ion concentration is greater than 0.8 m, the oligomers and fiber body instead inhibition of H 2 O 2 generate the effect. The paper also measured in the same concentration of copper ions (0.8 m), H 2 O 2 How much is three different Aβ aggregation system. The results showed that the presence of oligomers the H 2 O 2 Max. In this thesis, the bathocuproin (BC) experimental analysis of the interaction of three different aggregates of Aβ and copper ions Cu (I) generation. Cu (I) generated in the case of the experiments showed that the presence of oligomers up, followed by the monomer, then the fiber body. With different concentrations of ascorbic acid and copper ions as the control group, in the case does not exist Conformation, by H 2 DCF-DA experiments (the detection the H 2 O 2 ) and BC experiments (detection of Cu (I)) found that the generation of Cu (I) and H 2 O 2 generated between a positive Relevance. Therefore, we propose: moderate folding and aggregation conformation (oligomers) on the formation of Cu (I) and H 2 O 2 of produce has a crucial effect. This may be just what oligomers one of the reasons that are more toxic than the other two aggregates.

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