title: Unraveling the role of hydrogen peroxide in α-synuclein aggregation using an ultrasensitive nanoplasmonic probe.
abstract: Aggregation of α-Synuclein (α-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 α-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 α-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 α-Syn in vitro, whereas the contribution from endogenously secreted H2O2 is negligible.
authors.affiliation: Division of Physical Biology and Bioimaging Centre, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences , Shanghai 201800, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Kun
authors.initials: K
authors.lastname: Li
authors.forename: Weiwei
authors.initials: W
authors.lastname: Qin
authors.forename: Bing
authors.initials: B
authors.lastname: Zhu
authors.forename: Ziang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Jiye
authors.initials: J
authors.lastname: Shi
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.forename: Chunhai
authors.initials: C
authors.lastname: Fan
authors.forename: Di
authors.initials: D
authors.lastname: Li
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D057809:HEK293 Cells; D006735:Horseradish Peroxidase / Q000737:chemistry; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis / Q000378:metabolism*; D053768:Metal Nanoparticles / Q000737:chemistry*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000378:metabolism; D058105:Polymerization; D066263:Protein Aggregation, Pathological / Q000378:metabolism*; D020349:Surface Plasmon Resonance / Q000379:methods*; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000814:Aniline Compounds; D051844:alpha-Synuclein; D006046:Gold; D004247:DNA; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; C023650:aniline