The Effect Of Chelators On The Dissociation Of Metal-Aβ40/42 Aggregates

Alzheimer’s Disease is the most common form of dementia.β-amyloid(Aβ) deposition is one of the important pathological features of Alzheimer’s disease. Some ions like Cu2+、Zn2+ could accelarate Aβpeptide aggregate to be insoluble precipitates. The deposition of extracellular Aβhas been suggested to be the cause of AD. We have synthesized two fluorescent chelating agents. They could disaggregate ion-Aβaggregates. We study the procedure by fluorescence spectroscopy, UV-visible spectroscopy, transmission electron microscopy, inverted flurescent microscopy et al. And test the cell toxicity by MTT.The main results including:1. We study the two ligands’fluorescence properties which including pH、solvents and various metal ions. We choice 10% ethanol, Tris-HCl buffer (pH 7.4) as the reaction system for most of the experiments. Two ligands specially respond on Cu2+ and Zn2+.2. By fluorescence method、BCA assay, we detect the depolymerization of Aβaggregates by the ligand. We found the ligands could chelate most of the ions in the aggregates which have only a small part depolymerized.3. From Transmission electron microscopy, we can see the ion-Aβaggregates have varying degrees of polymer depolymerization after react with ligands. Aβ40 have better depolymerizatin effect than AP42.4. Cell experiments confirmed that FC-11 can cross the cell membrane. From toxicity experiments, we found that FC-11-Cu2+、FC-12-Cu2+ have strong cytotoxicity. From the greatly enhanced cytotoxicity after Cu2+-Aβ40 effect with the ligand, it comfirmed that the ligand could chelat most of Cu2+ that complexed with Aβ.