Exploring the Impact of Glyoxal Glycation on β-Amyloid Peptide (Aβ) Aggregation in Alzheimer's Disease

Kai Wei Hu, Hsiu Fang Fan, Han Chen Lin, Jian Wei Huang, Yu Chieh Chen, Cai Ling Shen, Yao Hsiang Shih, Ling Hsien Tu*

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

摘要

Alzheimer's disease (AD) is characterized by the presence of extracellular senile plaques formed by β-amyloid (Aβ) peptides in the patient's brain. Previous studies have shown that the plaques in the AD brains are colocalized with the advanced glycation end products, which is mainly formed from a series of nonenzymatic reactions of proteins with reducing sugars or reactive dicarbonyls. Glycation was also demonstrated to increase the neurotoxicity of the Aβ peptides. To clarify the impact of glycation on Aβ aggregation, we synthesized two glycated Aβ42 peptides by replacing Lys16 and Lys28 with Nϵ-carboxymethyllysine respectively to mimic the occurrence of protein glycation. Afterward, we monitored the aggregation kinetics and conformational change for two glycated peptides. We also used fluorescence correlation spectroscopy to probe the early stage of peptide oligomerization and tested their abilities in copper binding and reactive oxygen species production. Our data show that glycation significantly slows down the aggregation process and induces more cytotoxicity especially at position 28. We speculated that the higher toxicity might result from a relatively stable oligomeric form of peptide and not from ROS production. The data shown here emphasized that glycated proteins would be an important therapeutic target in AD treatments.

原文英語
頁(從 - 到)5559-5571
頁數13
期刊Journal of Physical Chemistry B
125
發行號21
DOIs
出版狀態已發佈 - 2021 六月 3

ASJC Scopus subject areas

  • 物理與理論化學
  • 表面、塗料和薄膜
  • 材料化學

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