期刊
ACS CHEMICAL NEUROSCIENCE
卷 13, 期 8, 页码 1178-1186出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.1c00703
关键词
pyrroloquinoline quinone (PQQ); ?-synuclein; copper(II); ?-synuclein-119; antioxidant; Parkinson?s disease
资金
- Canada Research Chair Tier-2 award [950-231116]
- Ontario Ministry of Research and Innovation [35272]
- Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN-2020-07164]
- Canada Foundation for Innovation [35272]
Parkinson's disease (PD) is associated with the aggregation and misfolding of α-synuclein (α-syn) protein. A proof-of-concept study found that pyrroloquinoline quinone (PQQ) can effectively prevent ROS formation and fibrillation of α-syn-119 in the presence of Cu(II), suggesting PQQ as a potential multitarget therapeutic agent for PD.
Parkinson's disease (PD) is associated with the aggregation and misfolding of a-synuclein (a-syn) protein in dopaminergic neurons. The misfolding process is heavily linked tocopper dysregulation in PD. Experimental evidence supports the hypothesis that the co-presence of Cu(II) and alpha-syn facilitates the aggregation of alpha-syn, affecting the pathologicaldevelopment of PD. Recent literature has shown that pyrroloquinoline quinone (PQQ)contains strong neuroprotective activity by reducing the reactive oxygen species (ROS)production by alpha-syn. Despite these known facts, minimal studies have been done on theantioxidant effect of PQQ against ROS formation in the presence of Cu(II) and alpha-syn-119.Thus, it is of great significance to study the interaction between all three components, PQQ,Cu(II), and alpha-syn-119. In this proof-of-concept study, a variety of chemical techniques wereemployed to examine the antioxidant effect of PQQ on ROS that alpha-syn-119 produced in thepresence of Cu(II). Our results showed that PQQ effectively prevented ROS formation in SH-SY5Y human differentiated neuronal cells. Thioflavin T (ThT)fluorescence assay, circulardichroism (CD) spectroscopy, and transmission electron microscopy (TEM) were applied, where PQQ was able to actively preventfibrillation of alpha-syn-119 in the presence of Cu(II). Thisfinding was further confirmed using electrochemical impedance spectroscopy(EIS), where the binding of PQQ to the alpha-syn-119 suppressed the aggregation process on the electrode surface. With theseencouraging results, we envisage that PQQ and its derivatives can be a promising candidate for further studies as a multitargettherapeutic agent toward PD therapy
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据