Department of Biology, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
Department of Physics & Astronomy, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
Molecules. 2018 Nov 27;23(12):3089. doi: 10.3390/molecules23123089.
Healthcare has advanced significantly, bringing with it longer life expectancies and a growing population of elders who suffer from dementia, specifically Alzheimer's disease (AD). The amyloid beta (Aβ) peptide has been implicated in the cause of AD, where the peptides undergo a conformational change and form neurotoxic amyloid oligomers which cause neuronal cell death. While AD has no cure, preventative measures are being designed to either slow down or stop the progression of this neurodegenerative disease. One of these measures involves dietary supplements with polyunsaturated fatty acids such as docosahexaenoic acid (DHA). This omega-3 fatty acid is a key component of brain development and has been suggested to reduce the progression of cognitive decline. However, different studies have yielded different results as to whether DHA has positive, negative, or no effects on Aβ fibril formation. We believe that these discrepancies can be explained with varying concentrations of DHA. Here, we test the inhibitory effect of different concentrations of DHA on amyloid fibril formation using atomic force microscopy. Our results show that DHA has a strong inhibitory effect on Aβ fibril formation at lower concentrations (50% reduction in fibril length) than higher concentrations above its critical micelle concentration (70% increase in fibril length and three times the length of those at lower concentrations). We provide evidence that various concentrations of DHA can play a role in the inhibitory effects of amyloid fibril formation in vitro and help explain the discrepancies observed in previous studies.
医疗保健取得了重大进展,带来了更长的预期寿命和越来越多患有痴呆症(特别是阿尔茨海默病)的老年人。淀粉样蛋白β(Aβ)肽与阿尔茨海默病的病因有关,其中肽经历构象变化并形成神经毒性淀粉样寡聚物,导致神经元细胞死亡。虽然阿尔茨海默病尚无治愈方法,但正在设计预防措施来减缓或阻止这种神经退行性疾病的进展。其中一种措施涉及含有多不饱和脂肪酸(如二十二碳六烯酸(DHA))的膳食补充剂。这种ω-3 脂肪酸是大脑发育的关键组成部分,并且已被证明可以减缓认知能力下降的进展。然而,不同的研究对于 DHA 是否对 Aβ 纤维形成有积极、消极或无影响得出了不同的结果。我们认为这些差异可以用 DHA 的不同浓度来解释。在这里,我们使用原子力显微镜测试了不同浓度的 DHA 对淀粉样纤维形成的抑制作用。我们的结果表明,DHA 在较低浓度(纤维长度减少 50%)下对 Aβ 纤维形成具有很强的抑制作用,而在高于其临界胶束浓度(纤维长度增加 70%,并且长度是低浓度下的三倍)的浓度下则没有这种抑制作用。我们提供的证据表明,不同浓度的 DHA 可以在体外抑制淀粉样纤维形成中发挥作用,并有助于解释以前研究中观察到的差异。