The Interaction Of Fluorescent Chelator And Metal-Aβ Aggregates

With the population aging, Alzheimer’s disease (AD) has been seriously endanger the health of the old people, while caused enormous burden on the family and society. It has been paying attention by many countries’people in the world.β-amyloid peptide (Aβ), the aggregates incidence of AD is considered to be one of the factors playing an important role. Aβ40 is the major Aβspecies secreted by cultured neurons accounted for 90% of Aβ, however, more likely 10% of Aβ42 occurrence of amyloid aggregates in senile plaques is the main form of Aβ. Found by the metal ions Cu2+、Zn2+-induced Aβ40/42 aggregation process is reversible, metal chelating agents can be used to control the production of aggregates Aβ40/42 disassembly, hence the using of metal chelating ligands to reduce the damage of metal ions has become an important strategy for the treatment of AD.Based on our research group has synthesized a series of feature recognition and disassembly of fluorescence chelators (FC-X), with initial screening of FC-9、FC-10 of fluorescent chelating ligands and metal-Aβ40/42 aggregates interactions, the results obtained are as follows:1. Fluorescence spectroscopy results showed that FC-9、FC-10 in 8 days and the pH 3-8 range relatively stable within the fluorescence, the fluorescence intensity reflects the typical solvent-dependent; all kinds of metal ions on the FC-9 little affect on the fluorescence, Cu2+、Fe3+、Co2+、Ni2+ on the FC-10 are part of the fluorescence quenching, Cu2+ quenching of its greatest extent.2. Not only FC-9、FC-10 is aggregation of metal-AP40/42 a certain degree of recognition, but also makes the metal-Aβ40/42 aggregates depolymerization. Depolymerization detection experiments from the BCA protein concentration、turbidity、right-angle light scattering、gel electrophoresis and other experimental results to be confirmed.3. Transmission electron microscopy and fluorescence microscope results further demonstrated the FC-9、FC-10 can make the metal-Aβaggregates depolymerization, and observed their morphologys; circular dichroism test results show that the FC-9、FC-10 can make the metal-Aβchanged in the secondary structure of aggregates. 4. Cell membrane results show that FC-9、FC-10 cross the cell membrane, but don’t into the nucleus; cytotoxicity by MTT method experimental results show that the FC-9、FC-10 in the presence Cu+-Aβ40 aggregates slightly decrease toxicity, cell viability increased slightly, FC-9、FC-10 can be suppressed to some extent by the Cu2+-Aβ40 aggregates the toxicity...