Spectral Study On The Interaction Of Copper(Ⅱ),Zinc(Ⅱ) With Aβ

Alzheimer disease (AD) is a neurodegenerative disorder of the central nervous system. It is recognized as a major public health problem having a severe impact on human beings. A major pathological characters is that senile plaques (SPs) occur in the brains of patients. SPs are neurotoxic and their extensive depositions cause neurodegeneration. The studies shows that Amyloid β -peptides(A β s)aggregate and accumulate,moreover,colocalize with numerous other associated protein and nonprotein components to form SPs.There are many factors to induce the A β aggregation. It has been reported that metal ions have a direct role in the aggregation of A β ,however,no clear data reveal their binding sites on Aβ .Zinc and copper are essential trace metals in normal bain.Here,we have pay more attention to the effect of metal ions inducing the aggregation of A β .It has been reported that Copper(II) ion not only induces A β aggregation but also forms soluble complexes with A β peptide in vitro. The possible binding modes of Cu²⁺ in A β (10—21) has been studied by molecular modeling method.The correlative amino acides are Tyr, His, Gln, Glu.Using spectrophotometry,the stability constants of copper ( II ) ion and amino acids in A β ( 10 — 20 ) were calculated respectively.we also preliminarily estimated the sequence of binding ability of Copper(II) Ion with Amino Acids in Aβ .The sequence of binding ability is : Lys >Tyr > His > Gln^Leu > Glu > Val > Phe.According to this sequence,We could preliminarily estimate that the preliminary binding sates of copper(II) ion in A β peptide should also accord with this sequence. This result is contensist with that of molecular modeling method but Lys.It will provide useful information to discuss the binding site of copper(II) ion in A β peptide.Zn²⁺ ion induces significant A β aggregation at nearly physiological concentrations in virtro. The possible binding modes in soluble andinsoluble complex of Zn2+in A P (10-21) aggregation has been studied by molecular modeling method. Upon the research of experiments and theory, we made A {3 (10—21) for the target peptide and studied the influences of the different concentration of Zn2+ in A 3 aggregation, we demonstrated that Zn2+ induced A0 (10-21) aggregate rapidly. Our findings suggest that the region 10-21 to be the minimal fragment of zinc-binding domain...