PRO OXIDANT ACTIVITY OF BETA AMYLOID PEPTIDES

已知，对β-淀粉样前体蛋白进行细胞内蛋白分解处理可产生含有40或42个残基的β-淀粉样多肽[A(Beta)]，这些残基是阿尔茨海默病中发现的老年斑的主要成分，已被证明对培养的神经细胞有毒性，并在体外促进氧化蛋白损伤。由于A(Beta)-42肽与铜具有紧密的结合部位，我们正在研究A(Beta)的促氧化活性可能是由于金属(铜)催化的反应。初步研究结果证实，商业制剂A(Beta)-42而不是A(Beta)-40含有大量铜，而且进一步添加铜可增强其氧化蛋白质的能力。这些结果表明，A(β)促进的毒性可能与铜介导的自由基化学有关。进一步的研究旨在测试这一可能性。

Intracellular proteolytic processing of the beta-amyloid precursor protein is known to yield beta-amyloid peptides [A(beta)] containing 40 or 42 residues that are major constituents of the senile plaques found in Alzheimer's disease and which have been shown to be toxic to cultured neuronal cells and to promote oxidative protein damage in vitro. Because the A(beta)-42 peptide possesses a tight binding site for copper, we are examining the possibility that the pro-oxidant activity of A(beta) is due to metal (copper)-catalyzed reactions. Results of preliminary studies confirm that commercial preparations of A(beta)-42, but not A(beta)-40, contain significant amounts of copper and that its ability to oxidize proteins is enhanced by further addition of cupric copper. These results suggest that the A(beta)-promoted toxicity may involve copper-mediated free radical chemistry. Further studies are designed to test this possibility.