Klunk W E, Debnath M L, Koros A M, Pettegrew J W
Department of Psychiatry, University of Pittsburgh School of Medicine and Infectious Diseases, PA 15261, USA.
Life Sci. 1998;63(20):1807-14. doi: 10.1016/s0024-3205(98)00454-8.
Increasing evidence suggests that deposition of amyloid-beta (A beta) peptide leads to neurodegeneration in Alzheimer's disease. Congo red, a histologic dye that binds to amyloid has previously been shown to diminish the toxic effects of A beta in cell culture. Since Congo red is too highly charged to enter the brain in significant quantities, a lipophilic derivative, Chrysamine-G, was tested for the ability to attenuate A beta[25-35]-induced toxicity in PC12 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Chrysamine-G showed a concentration-dependent inhibition of A beta[25-35]-induced toxicity. This protective effect became significant at 0.2 microM, a concentration very close to the Ki for Chrysamine-G binding to synthetic A beta (0.37 microM). A decarboxy derivative of Chrysamine-G, which does not bind to A beta, also did not protect against A beta-induced toxicity. The protective effects of Chrysamine-G may relate to its ability to bind directly to A beta and may involve other post-binding effects as well.
越来越多的证据表明，β-淀粉样蛋白（Aβ）肽的沉积会导致阿尔茨海默病中的神经退行性变。刚果红是一种与淀粉样蛋白结合的组织学染料，此前已证明它能在细胞培养中减少Aβ的毒性作用。由于刚果红带电荷过高，无法大量进入大脑，因此使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定法，对一种亲脂性衍生物Chrysamine-G减弱Aβ[25-35]诱导的PC12细胞毒性的能力进行了测试。Chrysamine-G对Aβ[25-35]诱导的毒性表现出浓度依赖性抑制。这种保护作用在0.2微摩尔时变得显著，该浓度与Chrysamine-G与合成Aβ结合的解离常数（Ki，0.37微摩尔）非常接近。Chrysamine-G的一种脱羧衍生物不与Aβ结合，也不能预防Aβ诱导的毒性。Chrysamine-G的保护作用可能与其直接结合Aβ的能力有关，也可能涉及其他结合后的效应。
