SOURCES AND EFFECTS OF REACTIVE OXYGEN INTERMEDIATES IN THE BRAIN

德尔里奥·霍特加在1919年是第一个 认识到小胶质细胞的重要性。它们就是大脑 巨噬细胞或吞噬细胞，它们也释放活性氧 物种。它们的功能是清除不需要的细胞碎片和 也是为了杀死入侵的微生物。就会产生氧气爆发 由己糖单磷酸分流产生超氧化物 膜上的NADPH氧化酶产生负离子。佛波酯 醋酸盐(PMA)直接作用于这一机制。我们调查了 β淀粉样蛋白(A-β)对超氧化物生成的影响 激活的小胶质细胞的阴离子。A-β(1-40)来源于 淀粉样前体蛋白，含有约700个氨基酸。 富含半胱氨酸的部分含有一个可以降低铜含量的部位 离子到亚铜离子。A-β有一个胞外区，以及 膜结构域。我们在激活的仓鼠身上做了实验 小胶质细胞和人单核细胞来源的巨噬细胞与PMA， 研究发现，额外接触A-β(1-40)只会产生 少量的超氧阴离子。然而，当小胶质细胞 先用A-β，然后用PMA进行预涂或处理 活化时，超氧阴离子增加较多 制作。没有PMA，超氧化物的生成就会减少 在A-β(1-40)存在的情况下获得的值，这是 大于未启动和未受刺激的情况。这个 结论是，还有另一个地点对此负责 超氧化物生产。也许这个部位就是线粒体。在……里面 阿尔茨海默病，A-β(1-40)位于斑块中 周围，在那里它导致斑块中发现的静止的小胶质细胞 产生有害的活性氧物种，它可以攻击 神经系统中最脆弱的部分是突触。小胶质细胞 不能破坏斑块，因为它们由 贝塔褶皱薄片，只溶于甲酸。

Del Rio Hortega in 1919 was the first person to recognize the importance of microglia. They are the brain macrophages or phagocytes, which also release reactive oxygen species. Their function is to get rid of unwanted cellular debris and also to kill invading microorganisms. An oxygen burst is generated by the hexose monophosphatase shunt producing the superoxide anion by the NADPH oxidase at the membrane. Phorbol myristate acetate (PMA) acts directly on this mechanism. We investigated the effect of beta amyloid (A-beta) on the production of superoxide anion of activated microglia. A-beta (1-40) is derived from the amyloid precursor protein, which contains about 700 amino acids. The cysteine rich section contains a site which can reduce cupric ions to cuprous ions. A-beta has an extracellular domain as well as a membrane domain. We experimented on activated hamster microglia and human monocyte derived macrophages with PMA, and found that additional exposure to A-beta (1-40) produced only a small quantity of superoxide anion. However, when the microglia were primed or pretreated with A-beta followed by PMA activation, there was a larger increase in superoxide anion production. Without PMA, the superoxide production was reduced to the value obtained in the presence of A-beta (1-40), which was greater than the non-primed and non-stimulated case. The conclusion is that there is another site responsible for the superoxide production. Perhaps this site is the mitochondrion. In Alzheimer's disease, A-beta (1-40) is located in the plaque periphery, where it causes the resting microglia found in plaques to produce damaging reactive oxygen species, which can attack the most vulnerable part of the nervous system, the synapses. Microglia are not able to destroy the plaques because they are composed of beta pleated sheets, which are only soluble in formic acid.