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

作者:Yang, Aihua; Wang, Chenxuan; Song, Baomin; Zhang, Wendi; Guo, Yuanyuan; Yang, Rong; Nie, Guangjun; Yang, Yanlian; Wang, Chen
来源:Neuroscience Bulletin, 2017, 33(4): 405-412.
DOI:10.1007/s12264-017-0144-z

摘要

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