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Resveratrol-mediated cleavage of amyloid β1-42 peptide; potential relevance to Alzheimer’s disease
Neurobiology of Aging ( IF 4.2 ) Pub Date : 2020-10-01 , DOI: 10.1016/j.neurobiolaging.2020.04.012
Sarmad Al-Edresi 1 , Izzeddin Alsalahat 2 , Sally Freeman 2 , Harmesh Aojula 2 , Jeffrey Penny 2
Affiliation  

Aggregation of amyloid β1-42 (Aβ1-42) peptide within the brain is considered one of the main causes of the neuropathological changes associated with Alzheimer's disease. Resveratrol is a well-known antioxidant but has also been reported to bind to Aβ1-42 peptide, thereby reducing aggregation. However, little is known of the precise mechanism by which resveratrol reduces Aβ1-42 peptide aggregation. Using the thioflavin-T assay, the ability of resveratrol to reduce the extent of Aβ1-42 peptide aggregation was investigated. The findings of the present study demonstrate that interaction of resveratrol with Aβ1-42 peptide resulted in the cleavage of Aβ1-42 peptide into smaller fragments, as detected by matrix assisted laser desorption ionization-time of flight mass spectrometry. Atomic force microscopy analyses revealed Aβ1-42 peptide, under control conditions, aggregated into oligomers, protofibrils, and fibrils, whereas there was a distinct lack of these structures when Aβ1-42 peptide was incubated with resveratrol. Following 10 days incubation of Aβ1-42 peptide with resveratrol, particles with a mean z-height of 1.940 nm (range 0.675-3.275 nm) were observed, which are characteristic of shorter peptide species. In cell-based studies, resveratrol significantly reduced the cytotoxicity of Aβ1-42 peptide toward SH-SY5Y human neuroblastoma cells, suggesting a protective effect of the polyphenol. We therefore propose a novel mechanism by which resveratrol disrupts Aβ1-42 aggregation by mediating fragmentation of Aβ1-42 into smaller peptides, which have no propensity to aggregate further.

中文翻译:

白藜芦醇介导的 β1-42 淀粉样肽裂解;与阿尔茨海默病的潜在相关性

脑内淀粉样蛋白 β1-42 (Aβ1-42) 肽的聚集被认为是与阿尔茨海默病相关的神经病理学变化的主要原因之一。白藜芦醇是一种众所周知的抗氧化剂,但也有报道称它可以与 Aβ1-42 肽结合,从而减少聚集。然而,人们对白藜芦醇减少 Aβ1-42 肽聚集的确切机制知之甚少。使用硫代黄素-T 测定,研究了白藜芦醇降低 Aβ1-42 肽聚集程度的能力。本研究的结果表明,白藜芦醇与 Aβ1-42 肽的相互作用导致 Aβ1-42 肽裂解成更小的片段,如基质辅助激光解吸电离飞行时间质谱检测。原子力显微镜分析显示 Aβ1-42 肽,在对照条件下,聚集成寡聚体、原纤维和原纤维,而当 Aβ1-42 肽与白藜芦醇一起孵育时,这些结构明显缺失。Aβ1-42 肽与白藜芦醇孵育 10 天后,观察到平均 z 高度为 1.940 nm(范围 0.675-3.275 nm)的颗粒,这是较短肽种类的特征。在基于细胞的研究中,白藜芦醇显着降低了 Aβ1-42 肽对 SH-SY5Y 人神经母细胞瘤细胞的细胞毒性,表明多酚具有保护作用。因此,我们提出了一种新机制,白藜芦醇通过介导 Aβ1-42 断裂成更小的肽来破坏 Aβ1-42 聚集,这些肽没有进一步聚集的倾向。而当 Aβ1-42 肽与白藜芦醇一起孵育时,这些结构明显缺乏。Aβ1-42 肽与白藜芦醇孵育 10 天后,观察到平均 z 高度为 1.940 nm(范围 0.675-3.275 nm)的颗粒,这是较短肽种类的特征。在基于细胞的研究中,白藜芦醇显着降低了 Aβ1-42 肽对 SH-SY5Y 人神经母细胞瘤细胞的细胞毒性,表明多酚具有保护作用。因此,我们提出了一种新机制,白藜芦醇通过介导 Aβ1-42 断裂成更小的肽来破坏 Aβ1-42 聚集,这些肽没有进一步聚集的倾向。而当 Aβ1-42 肽与白藜芦醇一起孵育时,这些结构明显缺乏。Aβ1-42 肽与白藜芦醇孵育 10 天后,观察到平均 z 高度为 1.940 nm(范围 0.675-3.275 nm)的颗粒,这是较短肽种类的特征。在基于细胞的研究中,白藜芦醇显着降低了 Aβ1-42 肽对 SH-SY5Y 人神经母细胞瘤细胞的细胞毒性,表明多酚具有保护作用。因此,我们提出了一种新机制,白藜芦醇通过介导 Aβ1-42 断裂成更小的肽来破坏 Aβ1-42 聚集,这些肽没有进一步聚集的倾向。观察到平均 z 高度为 1.940 nm(范围 0.675-3.275 nm)的颗粒,这是较短肽类的特征。在基于细胞的研究中,白藜芦醇显着降低了 Aβ1-42 肽对 SH-SY5Y 人神经母细胞瘤细胞的细胞毒性,表明多酚具有保护作用。因此,我们提出了一种新机制,白藜芦醇通过介导 Aβ1-42 断裂成更小的肽来破坏 Aβ1-42 聚集,这些肽没有进一步聚集的倾向。观察到平均 z 高度为 1.940 nm(范围 0.675-3.275 nm)的颗粒,这是较短肽类的特征。在基于细胞的研究中,白藜芦醇显着降低了 Aβ1-42 肽对 SH-SY5Y 人神经母细胞瘤细胞的细胞毒性,表明多酚具有保护作用。因此,我们提出了一种新机制,白藜芦醇通过介导 Aβ1-42 断裂成更小的肽来破坏 Aβ1-42 聚集,这些肽没有进一步聚集的倾向。
更新日期:2020-10-01
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