PATHOLOGICAL PROTEINS IN SENILE PLAQUES
PATHOLOGICAL PROTEINS IN SENILE PLAQUES
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DOI：
10.1620/tjem.174.269
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发表时间：
1994-11-01
影响因子：
2.2
通讯作者：
MCGEER, EG
中科院分区：
文献类型：
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作者：
MCGEER, PL;KLEGERIS, A;MCGEER, EG
阿尔茨海默病的β-amploid蛋白沉积物，无论是弥漫性的还是合并的形式，都是许多细胞外蛋白的聚集体。据报道，至少有 35 种是老年斑的成分，其中大多数也出现在弥漫性沉积物中。这些蛋白质中有一半以上与免疫系统直接相关。由于弥漫性沉积物被认为是老年斑的前兆，因此定义导致转变的精确分子事件非常重要。弥漫性沉积物与老年斑一样存在补体调理成分、补体激活剂β-淀粉样蛋白、淀粉样蛋白P、凝血酶和载脂蛋白E。然而，老年斑还含有营养不良的神经突、激活的小胶质细胞的聚集体、膜攻击复合物的成分和膜攻击的抑制剂。复合物、凝聚素、保护素和玻连蛋白。小胶质细胞是专业的吞噬细胞，在激活时具有呼吸爆发装置。它产生细胞外超氧化物分子，然后形成额外的有毒产物，例如过氧化氢和羟基自由基。人们早就知道调理后的酵母聚糖是呼吸爆发系统的强大激活剂。我们发现这种激活可以被纳摩尔范围内的补体受体抗体抑制。氨苯砜和吲哚美辛这两种抗炎药可能对阿尔茨海默病具有治疗潜力，但抑制作用较弱（10(-4) M范围）。这些数据表明，补体激活到产生膜攻击复合物并产生呼吸爆发毒素的水平，可能是阿尔茨海默病的自毁机制的基础，并进一步暗示对这种激活的干预可能具有治疗可能性。
The beta-amploid protein deposits of Alzheimer disease, whether in diffuse or consoliated form, are an agglomeration of many extracellular proteins. At least 35 have been reported as components of senile plaques, most of which also occur in diffuse deposits. More than half of these proteins are directly associated with the immune system. Since diffuse deposits are believed to be the precursors of senile plaques, it is important to define the precise molecular events that lead to the transition. Diffuse deposits share with senile plaques the presence of opsonizing components of complement, the complement activators beta-amyloid protein, amyloid P, thrombin, and apolipoprotein E. However, senile plaques contain, in addition, dystrophic neurites, agglomerates of activated microglia, components of the membrane attack complex, and the inhibitors of the membrane attack. complex, clusterin, protectin and vitronectin. Microglial cells are professional phagocytes which possess the respiratory burst apparatus when activated. It produces extracellular superoxide molecules which can then form additional toxic products such as hydrogen peroxide and hydroxyl free radicals. It has long been known that opsonized zymosan is a powerful activator of the respiratory burst system. We found this activation could be inhibited by antibodies to complement receptors in the nanomolar range. Dapsone and indomethacin, two antiinflammatory agents that may have therapeutic potential in Alzheimer disease, mere weakly inhibitory (10(-4) M range). These data suggest that complement activation to a level where the membrane attack complex is generated, and respiratory burst toxins are produced, may underlie an autodestructive mechanism in Alzheimer disease, and further imply that intervention in this activation may have therapeutic possibilities.