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纳米红外分析脂类不饱和脂肪酸存在下形成的淀粉样β纤维。

Nano-infrared analysis of amyloid β fibrils formed in the presence of lipids with unsaturated fatty acids.

机构信息

Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, USA.

出版信息

Nanoscale. 2023 Dec 14;15(48):19650-19657. doi: 10.1039/d3nr05184f.

Abstract

Alzheimer's disease (AD) is characterized by progressive memory loss and serious impairment of cognitive abilities. AD is the most common cause of dementia, affecting more than 44 million people around the world. The hallmark of AD is amyloid plaques, extracellular deposits primarily found in the frontal lobe, that are composed of amyloid β (Aβ) aggregates. In this study, we utilized nano-infrared spectroscopy, also known as Atomic Force Microscopy Infrared (AFM-IR) spectroscopy to investigate the effect of unsaturated phospholipids on the rate of Aβ aggregation. We found that unsaturated phosphatidylcholine, phosphatidylserine, and cardiolipin strongly suppressed aggregation of Aβ. Furthermore, Aβ fibrils formed in the presence of such lipids exerted significantly lower cell toxicity compared to the protein aggregates formed in the lipid-free environment. These findings suggest that dietary changes linked to the increased consumption of unsaturated phospholipids could be considered as a potential therapeutic approach that can decelerate the progression of AD. These results also suggest that large unilamellar vesicles with unsaturated lipids can be used as potential therapeutics to delay the onset and decelerate the progression of AD.

摘要

阿尔茨海默病(AD)的特征是进行性记忆丧失和严重的认知能力损害。AD 是痴呆症最常见的原因,影响着全球超过 4400 万人。AD 的标志是淀粉样斑块,主要在额叶中发现的细胞外沉积物,由淀粉样 β(Aβ)聚集体组成。在这项研究中,我们利用纳米红外光谱,也称为原子力显微镜红外(AFM-IR)光谱来研究不饱和磷脂对 Aβ聚集速度的影响。我们发现不饱和磷脂酰胆碱、磷脂酰丝氨酸和心磷脂强烈抑制 Aβ的聚集。此外,与在无脂环境中形成的蛋白质聚集体相比,在存在这些脂质的情况下形成的 Aβ原纤维表现出明显较低的细胞毒性。这些发现表明,与增加不饱和磷脂消耗有关的饮食变化可以被认为是一种潜在的治疗方法,可以减缓 AD 的进展。这些结果还表明,具有不饱和脂质的大单室囊泡可用作潜在的治疗剂,以延迟 AD 的发作并减缓其进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdd/11034782/42781d3dbc00/nihms-1950067-f0001.jpg

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