Lee Joo-Yong, Friedman Jonathan E, Angel Itzchak, Kozak Alex, Koh Jae-Young
Department of Neurology, National Creative Research Initiative Center for the Study of CNS Zinc, College of Medicine, University of Ulsan, Seoul 138-736, South Korea.
Neurobiol Aging. 2004 Nov-Dec;25(10):1315-21. doi: 10.1016/j.neurobiolaging.2004.01.005.
Metals such as zinc, copper and iron contribute to aggregation of amyloid-beta (Abeta) protein and deposition of amyloid plaques in Alzheimer's disease (AD). We examined whether the lipophilic metal chelator DP-109 inhibited these events in aged female hAbetaPP-transgenic Tg2576 mice. Daily gavage administration of DP-109 for 3 months markedly reduced the burden of amyloid plaques and the degree of cerebral amyloid angiopathy in brains, compared to animals receiving vehicle treatment. Moreover, DP-109 treatment appeared to facilitate the transition of Abeta from insoluble to soluble forms in the cerebrum. These results further support the hypothesis that endogenous metals are involved in the deposition of aggregated Abeta in brains of AD patients, and that metal chelators may be useful therapeutic agents in the treatment of AD.
锌、铜和铁等金属会促使β-淀粉样蛋白（Aβ）聚集以及淀粉样斑块在阿尔茨海默病（AD）中沉积。我们研究了亲脂性金属螯合剂DP-109是否能在老年雌性hAβPP转基因Tg2576小鼠中抑制这些事件。与接受赋形剂处理的动物相比，每天经口灌胃给予DP-109 3个月可显著减轻大脑中淀粉样斑块的负担以及脑淀粉样血管病的程度。此外，DP-109处理似乎有助于大脑中Aβ从不溶性形式转变为可溶性形式。这些结果进一步支持了以下假说：内源性金属参与了AD患者大脑中聚集的Aβ沉积，并且金属螯合剂可能是治疗AD的有用治疗药物。
