Yu W H, Lukiw W J, Bergeron C, Niznik H B, Fraser P E
Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen's Park Crescent West, Ontario M5S 3H2, Toronto, Canada.
Brain Res. 2001 Mar 9;894(1):37-45. doi: 10.1016/s0006-8993(00)03196-6.
Metallothionein III (MT-III) is a functionally distinct member of the metallothionein family that displays neuroinhibitory activity and is involved in the repair of neuronal damage. Altered expression levels of MT-III have been observed in Alzheimer's disease (AD) which has led to suggestions that it could be a mitigating factor in AD-related neuronal dysfunction. However, conflicting results have been reported on this issue which may be due to methodological differences and/or sampling size. In the current study, we have assessed MT-III expression in a large number of AD cases through the quantification of mRNA as well as by immunohistochemistry and Western blotting using an MT-III specific antibody. The results of this comprehensive study indicate that the mononucleosome DNA encoding MT-III is occluded preventing transcription and that message levels are reduced by approximately 30%. In addition, protein levels were specifically decreased by approximately 55% in temporal cortex. These data support the conclusion that MT-III is significantly downregulated in AD and may contribute to the loss of its protective effects and/or repair functions that lead to an exacerbation of the pathogenic processes.
金属硫蛋白III（MT-III）是金属硫蛋白家族中功能独特的一员，具有神经抑制活性，并参与神经元损伤的修复。在阿尔茨海默病（AD）中已观察到MT-III表达水平的改变，这提示它可能是AD相关神经元功能障碍的一个缓解因素。然而，关于这个问题的报道结果相互矛盾，这可能是由于方法学差异和/或样本量的原因。在本研究中，我们通过mRNA定量以及使用MT-III特异性抗体进行免疫组织化学和蛋白质印迹分析，评估了大量AD病例中的MT-III表达。这项综合研究的结果表明，编码MT-III的单核小体DNA被封闭，阻止了转录，并且信使水平降低了约30%。此外，颞叶皮质中的蛋白质水平特异性降低了约55%。这些数据支持以下结论：MT-III在AD中显著下调，可能导致其保护作用和/或修复功能丧失，从而加剧致病过程。
