Only amyloidogenic intermediates of transthyretin induce apoptosis
Only amyloidogenic intermediates of transthyretin induce apoptosis
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DOI：
10.1016/s0006-291x(02)00465-5
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发表时间：
2002-06-07
影响因子：
3.1
通讯作者：
Lundgren, E
中科院分区：
文献类型：
--
作者：
Andersson, K;Olofsson, A;Lundgren, E
在阿尔茨海默病和家族性淀粉样变性多神经病变（FAP）等疾病中，淀粉样蛋白沉积与神经变性区域共定位。FAP与血浆转甲状腺素（TTR）突变有关。我们可以在这里显示TTR淀粉样突变体对人神经母细胞瘤细胞系的凋亡作用。过氧化氢酶可以阻断毒性，表明其依赖自由基的机制。毒性作用依赖于未能发挥凋亡反应的fap患者的聚集状态和意想不到的成熟原纤维。形态学研究揭示了毒性与未成熟淀粉样蛋白的存在之间的相关性。因此，我们可以证明毒性与原纤维形成的早期阶段有关，并提出成熟的全长原纤维代表一个惰性的结束阶段，这可能作为一种拯救机制。(C) 2002 Elsevier Science （USA）。版权所有。
In diseases like Alzheimer's disease and familial amyloidotic polyneuropathy (FAP) amyloid deposits co-localize with areas of neurodegeneration. FAP is associated with mutations of the plasma protein transthyretin (TTR). We can here show an apoptotic effect of amyloidogenic mutants of TTR on a human neuroblastoma cell line. Toxicity could be blocked by catalase indicating a free oxygen radical dependent mechanism. The toxic effect was dependent on the state of aggregation and unexpectedly mature fibrils from FAP-patients who failed to exert an apoptotic response. Morphological studies revealed a correlation between toxicity and the presence of immature amyloid. Thus, we can show that toxicity is associated with early stages of fibril formation and propose that mature full-length fibrils represent an inert end stage, which might serve as a rescue mechanism. (C) 2002 Elsevier Science (USA). All rights reserved.