title: Inhibition effects of tanshinone on the aggregation of α-synuclein.
abstract: Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Lewy bodies that are formed by the aggregated α-synuclein are a major pathological feature of PD. Salvia miltiorrhiza has been used as food and as a traditional medicine for centuries in China, with tanshinone I (TAN I) and tanshinone IIA (TAN IIA) as its major bioactive ingredients. Here, we investigated the effects of TAN I and TAN IIA on α-synuclein aggregation both in vitro and in a transgenic Caenorhabditis elegans PD model (NL5901). We demonstrated that TAN I and TAN IIA inhibited the aggregation of α-synuclein as demonstrated by the prolonged lag time and the reduced thioflavin-T fluorescence intensity; TAN I and TAN IIA also disaggregated preformed mature fibrils in vitro. Moreover, the presence of TAN I or TAN IIA affected the secondary structural transformation of α-synuclein from unstructured coils to β-sheets, and alleviated the membrane disruption caused by aggregated α-synuclein in vitro. Besides, the immuno-dot-blot assay indicated that TAN I and TAN IIA reduce the formation of oligomers and fibrils. We further found that TAN I and TAN IIA extended the life span of NL5901, a strain of transgenic C. elegans that expresses human α-synuclein, possibly by attenuating the aggregation of α-synuclein. Taken together, our results suggested that TAN I and TAN IIA may be explored further as potential candidates for the prevention and treatment of PD.
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, 430030, China. kunhunag2008@hotmail.com.
authors.forename: Kaige
authors.initials: K
authors.lastname: Ji
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, 430030, China. kunhunag2008@hotmail.com.
authors.forename: Yudan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, 430030, China. kunhunag2008@hotmail.com.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Yu
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, 430030, China. kunhunag2008@hotmail.com.
authors.forename: Zhuoyi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, 430030, China. kunhunag2008@hotmail.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Gong
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, 430030, China. kunhunag2008@hotmail.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Synergy Innovation Center of Biological Peptide Antidiabetics of Hubei Province, School of Life Science, Wuchang University of Technology, Wuhan, 430223, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, 430030, China. kunhunag2008@hotmail.com and Center for Biomedicine Research, Wuhan Institute of Biotechnology, Wuhan, 430075, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000187:drug effects; D003474:Curcumin; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D010300:Parkinson Disease; D017510:Protein Folding; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism
chemical_list: D045784:Abietanes; D051844:alpha-Synuclein; C021751:tanshinone; D003474:Curcumin