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

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 fibr...

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Bibliographic Details
Published in:Neuroscience bulletin 2017-08, Vol.33 (4), p.405-412
Main Authors: Yang, Aihua, Wang, Chenxuan, Song, Baomin, Zhang, Wendi, Guo, Yuanyuan, Yang, Rong, Nie, Guangjun, Yang, Yanlian, Wang, Chen
Format: Article
Language:English
Subjects:
Amyloid beta-Peptides - genetics
Amyloid beta-Peptides - metabolism
Amyloid beta-Peptides - ultrastructure
Amyloid beta-Protein Precursor - genetics
Amyloid beta-Protein Precursor - metabolism
Amyloid beta-Protein Precursor - toxicity
Anatomy
Anesthesiology
Animals
Animals, Genetically Modified
Biomedical and Life Sciences
Biomedicine
Caenorhabditis elegans
Cell Line, Tumor
Cell Survival - drug effects
Dose-Response Relationship, Drug
Human Physiology
Humans
Kinetics
Neuroblastoma - pathology
Neurology
Neurosciences
Original
Original Article
Pain Medicine
Peptide Fragments - genetics
Peptide Fragments - metabolism
Peptide Fragments - ultrastructure
Protein Aggregation, Pathological - chemically induced
Protein Aggregation, Pathological - genetics
Transfection
β-淀粉样蛋白
β淀粉样蛋白
体内
毒性
淀粉样前体蛋白
聚集体
衰减
认知功能障碍
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Summary: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.
ISSN:1673-7067
1995-8218
DOI:10.1007/s12264-017-0144-z