Inhibition of alpha-synuclein fibrillization by dopamine analogs via reaction with the amino groups of alpha-synuclein
文献类型：期刊论文
| 作者 | Li, HT; Lin, DH; Luo, XY; Zhang, F; Ji, LN; Du, HN; Song, GQ; Hu, J; Zhou, JW; Hu, HY |
| 刊名 | FEBS JOURNAL
 |
| 出版日期 | 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 |
| 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. |
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