Inhibition of alpha-synuclein fibrillization by dopamine analogs via reaction with the amino groups of alpha-synuclein

	Inhibition of alpha-synuclein fibrillization by dopamine analogs via reaction with the amino groups of alpha-synuclein
	Li, HT; Lin, DH; Luo, XY; Zhang, F; Ji, LN; Du, HN; Song, GQ; Hu, J; Zhou, JW; Hu, HY
刊名	FEBS JOURNAL
	2005
卷号	272 期号:14 页码:3661-3672
关键词	alpha-synuclein dopamine inhibition fibrillization Parkinson's disease
通讯作者	Hu, HY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Proteom, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,hyhu@sibs.ac.cn
英文摘要	Fibrillization of alpha-synuclein (alpha-Syn) is closely associated with the formation of Lewy bodies in neurons and dopamine (DA) is a potent inhibitor for the process, which is implicated in the causative pathogenesis of Parkinson's disease (PD). To elucidate any molecular mechanism that may have biological relevance, we tested the inhibitory abilities of DA and several analogs including chemically synthetic and natural polyphenols in vitro. The MS and NMR characterizations strongly demonstrate that DA and its analogs inhibit alpha-Syn fibrillization by a mechanism where the oxidation products (quinones) of DA analogs react with the amino groups of alpha-Syn chain, generating alpha-Syn-quinone adducts. It is likely that the amino groups of alpha-Syn undergo nucleophilic attack on the quinone moiety of DA analogs to form imino bonds. The covalently cross-linked alpha-Syn adducts by DA are primarily large molecular mass oligomers, while those by catechol and p-benzoquinone (or hydroquinone) are largely monomers or dimers. The DA quinoprotein retains the same cytotoxicity as the intact alpha-Syn, suggesting that the oligomeric intermediates are the major elements that are toxic to the neuronal cells. This finding implies that the reaction of alpha-Syn with DA is relevant to the selective dopaminergic loss in PD.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	PARKINSONS-DISEASE ; IN-VITRO ; TRANSPORTER ACTIVITY ; PROTEIN AGGREGATION ; ALZHEIMERS-DISEASE ; OXIDATIVE STRESS ; FIBRIL FORMATION ; MECHANISM ; BETA ; NEURODEGENERATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000230293100016
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1972]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Li, HT,Lin, DH,Luo, XY,et al. Inhibition of alpha-synuclein fibrillization by dopamine analogs via reaction with the amino groups of alpha-synuclein[J]. FEBS JOURNAL,2005,272(14):3661-3672.
APA	Li, HT.,Lin, DH.,Luo, XY.,Zhang, F.,Ji, LN.,...&Hu, HY.(2005).Inhibition of alpha-synuclein fibrillization by dopamine analogs via reaction with the amino groups of alpha-synuclein.FEBS JOURNAL,272(14),3661-3672.
MLA	Li, HT,et al."Inhibition of alpha-synuclein fibrillization by dopamine analogs via reaction with the amino groups of alpha-synuclein".FEBS JOURNAL 272.14(2005):3661-3672.