Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA.
J Alzheimers Dis. 2010;20(2):569-76. doi: 10.3233/JAD-2010-1394.
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-beta (Abeta) 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 AbetaPP Swedish mutant incubated with high levels of homocysteine had an increase in Abeta formation, but no change in Herp level. Finally, over-expression of Herp did not result in any significant modification of Abeta levels. We conclude that the Herp protein pathway is unlikely to be directly involved in the pro-amyloidotic effect of HHcy.
饮食诱导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反应性应激蛋白，已被证明通过与体外早老素相互作用增加淀粉样-β（Abeta）的形成。我们论文的目的是研究 Herp 在 HHcy 诱导的淀粉样变性中的功能作用。Tg2576 小鼠饮食诱导的 HHcy 继发淀粉样变性与 Herp 蛋白和 mRNA 水平的增加有关。相比之下，相同的饮食方案不会改变其他应激相关蛋白。与野生型动物相比，遗传性 HHcy 小鼠模型的大脑中 Herp 水平没有明显变化。用高浓度同型半胱氨酸孵育稳定过表达人 AbetaPP 瑞典突变体的细胞，Abeta 形成增加，但 Herp 水平没有变化。最后，过表达 Herp 并没有导致 Abeta 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 的促淀粉样变性作用。
