The Herp protein pathway is not involved in the pro-amyloidogenic effect of hyperhomocysteinemia.
The Herp protein pathway is not involved in the pro-amyloidogenic effect of hyperhomocysteinemia.
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DOI：
10.3233/jad-2010-1394
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Praticò D
中科院分区：
文献类型：
--
作者：
Zhuo JM;Kruger WD;Praticò D
饮食引起的高循环同型半胱氨酸水平，也称为高同型半胱氨酸血症（HHcy），与阿尔茨海默病样淀粉样变性的加速有关。Herp是一种同型半胱氨酸应答应激蛋白，已被证明通过与早老素在体外的相互作用增加淀粉样蛋白-β (a β)的形成。本文的目的是研究疱疹在hhcy诱导的淀粉样变中所起的功能作用。Tg2576小鼠中继发于饮食诱导的HHcy的淀粉样变性与Herp蛋白和mRNA水平的增加有关。相比之下，其他与压力相关的蛋白质没有被相同的饮食方案所改变。与野生型动物相比，基因诱导的HHcy小鼠模型的大脑没有表现出任何显著的疱疹水平变化。高水平同型半胱氨酸孵育下稳定过表达人Aβ pp瑞典突变体的细胞，Aβ形成增加，但Herp水平没有变化。最后，Herp的过表达并未导致Aβ水平的显著改变。我们得出结论，Herp蛋白途径不太可能直接参与HHcy的前淀粉样变作用。
Diet-induced high circulating levels of homocysteine, also known as hyper-homocysteinemia (HHcy), is associated with an acceleration of Alzheimer’s disease-like amyloidosis. Herp is a homocysteine-responsive stress protein, which has been shown to increase the formation of amyloid-β (Aβ) via interaction with presenilins in vitro. The aim of our paper was to investigate the functional role that Herp plays in HHcy-induced amyloidosis. Amyloidosis secondary to diet-induced HHcy in Tg2576 mice is associated with an increase of Herp protein and mRNA levels. By contrast, no other stress-related proteins are altered by the same diet regimen. Compared to wild type animals, brains from a genetically induced HHcy mouse model did not manifest any significant change in Herp levels. Cells stably over-expressing human AβPP Swedish mutant incubated with high levels of homocysteine had an increase in Aβ formation, but no change in Herp level. Finally, over-expression of Herp did not result in any significant modification of Aβ levels. We conclude that the Herp protein pathway is unlikely to be directly involved in the pro-amyloidotic effect of HHcy.