The correlation between neurotoxicity, aggregative ability and secondary structure studied by sequence truncated Aβ peptides
The correlation between neurotoxicity, aggregative ability and secondary structure studied by sequence truncated Aβ peptides
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DOI：
10.1016/j.febslet.2007.02.026
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发表时间：
2007-03-20
期刊：
影响因子：
3.5
通讯作者：
Chen, Y. C.
中科院分区：
文献类型：
--
作者：
Liao, M. Q.;Tzeng, Y. J.;Chen, Y. C.
聚集的β-淀粉样蛋白(Aβ)多肽在体外和体内都具有神经毒性并导致神经元死亡。尽管形成聚集体通常需要形成β-折叠结构，但神经毒性和AD序列之间的关系仍不清楚。为了探索Aβ序列、二级结构、聚集能力和神经毒性之间的相关性，我们使用了全长和片段截短的Aβ多肽。结合光谱和细胞技术，我们证明了神经毒性和聚集能力是相关的，而这些特征与二级结构之间的关系并不显著。疏水的C末端，特别是17-21、25-35和41-42的氨基酸，是神经毒性和聚集的主要区域。删除残基17-21、25-35或41-42可显著降低毒性。另一方面，在22-24位或36-40位截断多肽对其毒性和聚集能力影响不大。虽然N-末端残基1-16可能在神经毒性和聚集中不起主要作用，但缺乏N-末端片段Aβ多肽(例如Aβ17-35)不会表现出全长或17-21，25-35截短的Aβ多肽的神经毒性。(C)2007年欧洲生化学会联合会。爱思唯尔出版，版权所有。
Aggregated beta-amyloid (A beta) peptides are neurotoxic and cause neuronal death both in vitro and in vivo. Although the formation of a beta-sheet structure is usual required to form aggregates, the relationship between neurotoxicity and the AD sequence remains unclear. To explore the correlation between A beta sequence, secondary structure, aggregative ability, and neurotoxicity, we utilized both full-length and fragment-truncated A beta peptides. Using a combination of spectroscopic and cellular techniques, we demonstrated that neurotoxicity and aggregative ability are correlated while the relationship between these characteristics and secondary structure is not significant. The hydrophobic C-terminus, particularly the amino acids of 17-21, 25-35, and 41-42, is the main region responsible for neurotoxicity and aggregation. Deleting residues 17-21, 25-35 or 41-42 significantly reduced the toxicity. On the other hand, truncation of the peptides at either residues 22-24 or residues 36-40 had little effect on toxicity and aggregative ability. While the N-terminal residues 1-16 may not play a major role in neurotoxicity and aggregation, a lack of N-terminal fragment A beta peptide, (e.g. A beta 17-35), does not display the neurotoxicity of either full-length or 17-21, 25-35 truncated A beta peptides. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.