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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)5559-5571
Number of pages13
JournalJournal of Physical Chemistry B
Volume125
Issue number21
DOIs
Publication statusPublished - 2021 Jun 3

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

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