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 incl...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.展开更多
Protein fibrillation is recognized as an attractive strategy to broaden and improve the function of food proteins.This research investigated the influence of different NaCl concentrations(0-210 mM)on the thermal aggre...Protein fibrillation is recognized as an attractive strategy to broaden and improve the function of food proteins.This research investigated the influence of different NaCl concentrations(0-210 mM)on the thermal aggregation behavior of rice proteins(RP)at pH 2.0.Under lower(<100 mM)and higher(>100 mM)NaCl concentrations,RP formed aggregates with different sizes and structures.At lower concentrations,the zeta-potential of RP increased from 14.3 mV to 22.8 mV during incubation,indicating that the electrostatic repulsion of RP was enhanced and numerous positively charged building blocks were generated.The circular dichroism(CD)results indicated that the native structure of RP was destroyed after heating at 90℃ for 24 h,and a secondary structure dominated byβ-sheets(more than 50%)was formed.Proteins formed long fibrils after 24 h heating,as observed by atomic force microscope(AFM).However,at higher NaCl concentrations,the hydrophobic interaction was the dominant force due to electrostatic shielding.The protein aggregated randomly to form amorphous aggregates with particle sizes over 600 nm.This study will provide a new insight of RP-based fibrils in food application.展开更多
基金supported by the National Natural Science Foundation of China(91127043,31600803,and 21273051)
文摘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.
基金support for this research was provided by the National Natural Science Foundation of China(No.32072263)Jiangsu rice green production and intensive processing technology integration innovation and demonstration application(No.BE2019395)+2 种基金the Key R&D Program of Jiangsu Province(BE202113592-2)the Fundamental Research Funds for the Central Universities(JUSRP622010)Agricultural Research Outstanding Talents Training Program(13210291).
文摘Protein fibrillation is recognized as an attractive strategy to broaden and improve the function of food proteins.This research investigated the influence of different NaCl concentrations(0-210 mM)on the thermal aggregation behavior of rice proteins(RP)at pH 2.0.Under lower(<100 mM)and higher(>100 mM)NaCl concentrations,RP formed aggregates with different sizes and structures.At lower concentrations,the zeta-potential of RP increased from 14.3 mV to 22.8 mV during incubation,indicating that the electrostatic repulsion of RP was enhanced and numerous positively charged building blocks were generated.The circular dichroism(CD)results indicated that the native structure of RP was destroyed after heating at 90℃ for 24 h,and a secondary structure dominated byβ-sheets(more than 50%)was formed.Proteins formed long fibrils after 24 h heating,as observed by atomic force microscope(AFM).However,at higher NaCl concentrations,the hydrophobic interaction was the dominant force due to electrostatic shielding.The protein aggregated randomly to form amorphous aggregates with particle sizes over 600 nm.This study will provide a new insight of RP-based fibrils in food application.
