铜暴露对阿尔茨海默病淀粉样蛋白病理的初步研究。
A Preliminary Study of Cu Exposure Effects upon Alzheimer's Amyloid Pathology.
机构信息
Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
出版信息
Biomolecules. 2020 Mar 6;10(3):408. doi: 10.3390/biom10030408.
A large body of evidence indicates that dysregulation of cerebral biometals (Fe, Cu, Zn) and their interactions with amyloid precursor protein (APP) and Aβ amyloid may contribute to the Alzheimer's disease (AD) Aβ amyloid pathology. However, the molecular underpinnings associated with the interactions are still not fully understood. Herein we have further validated the exacerbation of Aβ oligomerization by Cu and HO in vitro. We have also reported that Cu enhanced APP translations via its 5' untranslated region (5'UTR) of mRNA in SH-SY5Y cells, and increased Aβ amyloidosis and expression of associated pro-inflammatory cytokines such as MCP-5 in Alzheimer's APP/PS1 doubly transgenic mice. This preliminary study may further unravel the pathogenic role of Cu in Alzheimer's Aβ amyloid pathogenesis, warranting further investigation.
大量证据表明，脑生物金属（铁、铜、锌）的失调及其与淀粉样前体蛋白（APP）和 Aβ 淀粉样蛋白的相互作用可能导致阿尔茨海默病（AD）的 Aβ 淀粉样蛋白病理学。然而，与这些相互作用相关的分子基础仍不完全清楚。在此，我们进一步验证了 Cu 和 HO 在体外对 Aβ 寡聚化的加剧作用。我们还报告称，Cu 通过 SH-SY5Y 细胞中的 mRNA 的 5'非翻译区（5'UTR）增强 APP 的翻译，并增加 Aβ 淀粉样变性和相关促炎细胞因子如 MCP-5 在阿尔茨海默病 APP/PS1 双转基因小鼠中的表达。这项初步研究可能进一步揭示 Cu 在阿尔茨海默病 Aβ 淀粉样蛋白发病机制中的致病作用，值得进一步研究。
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