Ishii Kazuhiro, Klunk William E, Arawaka Shigeki, Debnath Manik L, Furiya Yoshiko, Sahara Naruhiko, Shoji Shin'ichi, Tamaoka Akira, Pettegrew Jay W, Mori Hiroshi
Department of Molecular Biology, Tokyo Institute of Psychiatry, Kamikitazawa, Tokyo 156-8585, Japan.
Neurosci Lett. 2002 Nov 15;333(1):5-8. doi: 10.1016/s0304-3940(02)00915-1.
The neurotoxicity of amyloid beta (Abeta) is widely believed to play a seminal role in neurodegeneration in Alzheimer's disease. We examined the effect of Chrysamine G (CG) on such neurotoxicity using the specific measurement of surviving neurons. CG was found to reduce the neurodegeneration induced by both the active short fragment of Abeta(25-35) and full-sized Abeta(1-40). In this study, we synthesized a new chemical compound from a monovalent structure of CG (hCG), with a lower affinity for Abeta, and compared its activity with that of CG. Both CG and hCG were found to be equally efficacious in reducing Abeta-induced neuronal death at a concentration of 0.1-1 microM, indicating that the mechanism of action for CG was not due to its chelating activity, but rather due to its anti-oxidant activity.
人们普遍认为，β-淀粉样蛋白（Aβ）的神经毒性在阿尔茨海默病的神经退行性变中起关键作用。我们使用存活神经元的特异性测量方法，研究了金胺G（CG）对这种神经毒性的影响。发现CG可减少由Aβ（25 - 35）活性短片段和全长Aβ（1 - 40）诱导的神经退行性变。在本研究中，我们从CG的单价结构合成了一种新的化合物（hCG），其对Aβ的亲和力较低，并将其活性与CG进行了比较。发现在0.1 - 1微摩尔浓度下，CG和hCG在减少Aβ诱导的神经元死亡方面同样有效，这表明CG的作用机制不是由于其螯合活性，而是由于其抗氧化活性。
