Thomas T, Thomas G, McLendon C, Sutton T, Mullan M
Roskamp Laboratories, Institute for Research in Psychiatry, University of South Florida, Tampa, 33613 USA.
Nature. 1996 Mar 14;380(6570):168-71. doi: 10.1038/380168a0.
Deposits of beta-amyloid are apparent in ageing and Alzheimer's disease, but the role of this peptide in neurodegeneration is unclear. The free-radical theory of ageing may also account for Alzheimer-type degeneration and consequently links between free-radical generation and beta-amyloid have been sought. We demonstrate here that beta-amyloid interacts with endothelial cells on blood vessels to produce and excess of superoxide radicals, with attendant alterations in endothelial structure and function. The superoxide radical can scavenge endothelium-derived relaxing factor and produce potent oxidizing agents, which can cause lipid peroxidation and other degenerative changes. The alterations in vascular tone and endothelial damage are prevented by the oxygen-radical-scavenging enzyme superoxide dismutase. These observations suggest a normal vasoactive role for beta-amyloid as well as a mechanism by which beta-amyloid may play a role in vascular abnormalities and neurodegeneration mediated by free radicals.
β-淀粉样蛋白沉积物在衰老和阿尔茨海默病中很明显，但这种肽在神经退行性变中的作用尚不清楚。衰老的自由基理论也可能解释阿尔茨海默型变性，因此人们一直在寻找自由基产生与β-淀粉样蛋白之间的联系。我们在此证明，β-淀粉样蛋白与血管内皮细胞相互作用，产生过量的超氧自由基，同时伴随内皮结构和功能的改变。超氧自由基可以清除内皮衍生的舒张因子并产生强效氧化剂，从而导致脂质过氧化和其他退行性变化。氧自由基清除酶超氧化物歧化酶可预防血管张力改变和内皮损伤。这些观察结果表明β-淀粉样蛋白具有正常的血管活性作用，以及β-淀粉样蛋白可能在自由基介导的血管异常和神经退行性变中发挥作用的机制。
