Webster S D, Tenner A J, Poulos T L, Cribbs D H
Department of Molecular Biology and Biochemistry, University of California Irvine, 92697-3900, USA.
Neurobiol Aging. 1999 May-Jun;20(3):297-304. doi: 10.1016/s0197-4580(99)00020-2.
In transgenic models of Alzheimer's disease (AD) neuronal loss has not been widely observed. The loss of neurons in AD may be due to chronic activation of complement (C') by beta-amyloid (A beta). A beta has been shown to activate C' by binding to a site on the C1q A-chain. The mouse A-chain sequence differs significantly from human, and a peptide based on the mouse A-chain sequence was ineffective at blocking activation of C' by A beta in contrast to the inhibition seen with the human peptide. Comparison of mouse and human serum showed that human C' was activated more effectively by A beta than was mouse C'. Therefore, additional genetic manipulations may be necessary to replicate in the murine model the inflammation and neurodegeneration that occur in AD.
在阿尔茨海默病（AD）的转基因模型中，尚未广泛观察到神经元丢失。AD中神经元的丢失可能是由于β-淀粉样蛋白（Aβ）对补体（C'）的慢性激活所致。已表明Aβ通过与C1q A链上的一个位点结合来激活C'。小鼠A链序列与人类有显著差异，基于小鼠A链序列的肽在阻断Aβ对C'的激活方面无效，这与人类肽所产生的抑制作用形成对比。对小鼠和人类血清的比较表明，Aβ对人类C'的激活比对小鼠C'更有效。因此，可能需要进行额外的基因操作，以便在小鼠模型中重现AD中发生的炎症和神经退行性变。
