Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, United States.
Department of Biomedical Engineering, Texas A&M University, College Station, Texas 77843, United States.
ACS Chem Neurosci. 2024 Sep 18;15(18):3344-3353. doi: 10.1021/acschemneuro.4c00275. Epub 2024 Sep 2.
Mono- and polyunsaturated fatty acids (FAs) are broadly used as food supplements. However, their effect on the aggregation of amyloidogenic proteins remains unclear. In this study, we investigated the effect of a large number of mono- and polyunsaturated, as well as fully saturated FAs on the aggregation of amyloid β (A) peptide. A progressive aggregation of this peptide is the expected molecular cause of Alzheimer's disease (AD), one of the most common neurodegenerative pathologies in the world. We found that arachidonic and stearic acids delayed the aggregation of Aβ1-42. Using Nano-Infrared spectroscopy, we found that FAs caused very little if any changes in the secondary structure of A oligomers and fibrils formed at different stages of protein aggregation. However, the analyzed mono- and polyunsaturated, as well as fully saturated FAs uniquely altered the toxicity of Aβ1-42 fibrils. We found a direct relationship between the degree of FAs unsaturation and toxicity of Aβ1-42 fibrils formed in their presence. Specifically, with an increase in the degree of unsaturation, the toxicity A/FA fibrils increased. These results indicate that fully saturated or monounsaturated FAs could be used to decrease the toxicity of amyloid aggregates and, consequently, decelerate the development of AD.
单不饱和脂肪酸和多不饱和脂肪酸（FAs）被广泛用作膳食补充剂。然而，它们对淀粉样蛋白原纤维聚集的影响尚不清楚。在这项研究中，我们研究了大量的单不饱和脂肪酸、多不饱和脂肪酸和完全饱和脂肪酸对淀粉样β（A）肽聚集的影响。这种肽的渐进聚集是阿尔茨海默病（AD）的预期分子原因，AD 是世界上最常见的神经退行性疾病之一。我们发现花生四烯酸和硬脂酸延迟了 Aβ1-42 的聚集。使用纳米红外光谱，我们发现 FAs 对在蛋白质聚集的不同阶段形成的 A 低聚物和原纤维的二级结构几乎没有影响。然而，分析的单不饱和脂肪酸、多不饱和脂肪酸和完全饱和脂肪酸独特地改变了 Aβ1-42 原纤维的毒性。我们发现 FAs 的不饱和度与它们存在时形成的 Aβ1-42 原纤维的毒性之间存在直接关系。具体来说，随着 FAs 不饱和度的增加，A/FA 原纤维的毒性增加。这些结果表明，完全饱和或单不饱和 FAs 可用于降低淀粉样聚集物的毒性，从而减缓 AD 的发展。
