Liao M Q, Tzeng Y J, Chang Lea Y X, Huang H B, Lin T H, Chyan C L, Chen Y C
Institute of Molecular and Cellular Biology, Tzu Chi University, Hualien 970, Taiwan.
FEBS Lett. 2007 Mar 20;581(6):1161-5. doi: 10.1016/j.febslet.2007.02.026. Epub 2007 Feb 20.
Aggregated beta-amyloid (Abeta) 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 Abeta sequence remains unclear. To explore the correlation between Abeta sequence, secondary structure, aggregative ability, and neurotoxicity, we utilized both full-length and fragment-truncated Abeta 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 Abeta peptide, (e.g. Abeta17-35), does not display the neurotoxicity of either full-length or 17-21, 25-35 truncated Abeta peptides.
聚集的β-淀粉样蛋白（Aβ）肽具有神经毒性，在体外和体内均可导致神经元死亡。虽然通常需要形成β-折叠结构才能形成聚集体，但神经毒性与Aβ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肽。通过结合光谱学和细胞技术，我们证明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位的氨基酸，是负责神经毒性和聚集的主要区域。删除17-21、25-35或41-42位的残基可显著降低毒性。另一方面，在22-24位或36-40位截断肽对毒性和聚集能力影响很小。虽然N末端的1-16位残基可能在神经毒性和聚集中不起主要作用，但缺乏N末端片段的Aβ肽（例如Aβ17-35）不表现出全长或17-21、25-35截短的Aβ肽的神经毒性。
