Unraveling the Role of Hydrogen Peroxide in 伪-Synuclein Aggregation Using an Ultrasensitive Nanoplasmonic Probe

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• 作者：Yan Xu ; Kun Li ; Weiwei Qin ; Bing Zhu ; Ziang Zhou ; Jiye Shi ; Kun Wang ; Jun Hu ; Chunhai Fan ; Di Li
• 刊名：Analytical Chemistry
• 出版年：2015
• 出版时间：February 3, 2015
• 年：2015
• 卷：87
• 期：3
• 页码：1968-1973
• 全文大小：377K
• ISSN：1520-6882

文摘

Aggregation of 伪-Synuclein (伪-Syn) in Lewy bodies is largely responsible for the demise and death of dopamine neurons. Oxidative stress associated with the aggregation-induced oxidative damage is considered as a possible origin of the toxicity. However, the cellular mechanism of H₂O₂ in the aggregation of 伪-Syn remains a debate, i.e., whether the aggregation is caused by endogenously secreted or exogenous H₂O₂ from upstream. Here, we report on the development of an ultrasensitive plasmonic assay with a designed nanoplasmonic probe to unravel the role of H₂O₂ in the aggregation of 伪-Syn. The nanoplasmonic probe is composed of a Au nanoparticle with surface-attached double-stranded DNA and horseradish peroxidase (HRP). In the presence of H₂O₂, HRP initiates the polymerization of aniline, which in turn results in the in situ formation of a layer of conducting polymer on the nanoplasmonic probe. By monitoring the associated plasmonic response, we can sensitively detect H₂O₂ with a remarkably low detection limit of 8 nM. With this ultrasensitive plasmonic assay, we find that exogenous H₂O₂ plays a dominant role for the aggregation of 伪-Syn in vitro, whereas the contribution from endogenously secreted H₂O₂ is negligible.