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Neuroscience Bulletin

, Volume 33, Issue 4, pp 405–412 | Cite as

Attenuation of β-Amyloid Toxicity In Vitro and In Vivo by Accelerated Aggregation

  • Aihua Yang
  • Chenxuan Wang
  • Baomin Song
  • Wendi Zhang
  • Yuanyuan Guo
  • Rong Yang
  • Guangjun Nie
  • Yanlian Yang
  • Chen Wang
Original Article

Abstract

Accumulation and aggregation of β-amyloid (Aβ) peptides result in neuronal death, leading to cognitive dysfunction in Alzheimer’s disease. The self-assembled Aβ molecules form various intermediate aggregates including oligomers that are more toxic to neurons than the mature aggregates, including fibrils. Thus, one strategy to alleviate Aβ toxicity is to facilitate the conversion of Aβ intermediates to larger aggregates such as fibrils. In this study, we designed a peptide named A3 that significantly enhanced the formation of amorphous aggregates of Aβ by accelerating the aggregation kinetics. Thioflavin T fluorescence experiments revealed an accelerated aggregation of Aβ monomers, accompanying reduced Aβ cytotoxicity. Transgenic Caenorhabditis elegans over-expressing amyloid precursor protein exhibited paralysis due to the accumulation of Aβ oligomers, and this phenotype was attenuated by feeding the animals with A3 peptide. These findings suggest that the Aβ aggregation-promotion effect can potentially be useful for developing strategies to reduce Aβ toxicity.

Keywords

Aβ Alzheimer’s disease Aggregation Aβ oligomer Amorphous aggregate Cell death C. elegans β-sheet 

Notes

Acknowledgements

We gratefully acknowledge Prof. Bai Lu of Tsinghua University for his help and thoughtful suggestions on the manuscript. This work was supported by the National Natural Science Foundation of China (91127043, 31600803, and 21273051).

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Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer Science+Business Media Singapore 2017

Authors and Affiliations

  • Aihua Yang
    • 1
  • Chenxuan Wang
    • 1
  • Baomin Song
    • 1
  • Wendi Zhang
    • 1
  • Yuanyuan Guo
    • 1
  • Rong Yang
    • 1
  • Guangjun Nie
    • 1
  • Yanlian Yang
    • 1
  • Chen Wang
    • 1
  1. 1.National Center for Nanoscience and TechnologyBeijingChina

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