Expression of metallothionein-I, -II, and -III in Alzheimer disease and animal models of neuroinflammation

Expression of metallothionein-I, -II, and -III in Alzheimer disease and animal models of neuroinflammation
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DOI:
10.1177/153537020623100902
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发表时间:
2006-10-01
影响因子:
3.2
通讯作者:
Ortega-Aznar, Arantxa
Ortega-Aznar, Arantxa
中科院分区:
医学4区
文献类型:
--
作者:
Hidalgo, Juan;Penkowa, Milena;Ortega-Aznar, Arantxa

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近年来,越来越清楚的是,金属硫蛋白(MT)家族的蛋白质是重要的神经生物学。MT-I和MT-II通常被神经炎症显著上调。MT-III的结果不太清楚。MT也可能与人类神经病理学有关。在阿尔茨海默病(AD),一种主要的神经退行性疾病,明确的迹象,炎症和氧化应激检测与淀粉样斑块。此外,在这些斑块中表达凋亡标志物的细胞数量也显著增加。正如预期的那样,MT-I和MT-II免疫染色在斑块周围的细胞中显著增加,与星形细胞增多和小胶质细胞增生以及淀粉样蛋白沉积引起的氧化应激增加一致。相比之下,MT-III基本上保持不变,这与AD的一些但不是所有研究一致。原位杂交产生AD淀粉样蛋白沉积的转基因小鼠模型,表达携带瑞典K670 N/M671 L突变的人AD前体蛋白的Tg 2576小鼠,与人脑中的结果一致。总的来说,这些和其他研究强烈表明MT-I,MT-II和MT-III在脑生理学中的特定作用。
In recent years it has become increasingly clear that the metallothionein (MT) family of proteins is important in neurobiology. MT-I and MT-II are normally dramatically up-regulated by neuroinflammation. Results for MT-III are less clear. MTs could also be relevant in human neuropathology. In Alzheimer disease (AD), a major neurodegenerative disease, clear signs of inflammation and oxidative stress were detected associated with amyloid plaques. Furthermore, the number of cells expressing apoptotic markers was also significantly increased in these plaques. As expected, MT-I and MT-II immunostaining was dramatically increased in cells surrounding the plaques, consistent with astrocytosis and microgliosis, as well as the increased oxidative stress elicited by the amyloid deposits. MT-III, in contrast, remained essentially unaltered, which agrees with some but not all studies, of AD. In situ hybridization results in a transgenic mouse model of AD amyloid deposits, the Tg2576 mouse, which expresses human AD precursor protein harboring the Swedish K670N/M671L mutations, are in accordance with results in human brains. Overall, these and other studies strongly suggest specific roles for MT-I, MT-II, and MT-III in brain physiology.