Khatua Prabir, Jana Asis K, Hansmann Ulrich H E
Department of Chemistry & Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, United States.
ACS Omega. 2021 Feb 17;6(8):5795-5804. doi: 10.1021/acsomega.0c06211. eCollection 2021 Mar 2.
While Alzheimer's disease is correlated with the presence of Aβ fibrils in patient brains, the more likely agents are their precursors, soluble oligomers that may form pores or otherwise distort cell membranes. Using all-atom molecular dynamics simulation, we study how the presence of fatty acids such as lauric acid changes the stability of pore-forming oligomers built from three-stranded Aβ chains. Such a change would alter the distribution of amyloids in the fatty acid-rich brain environment and therefore could explain the lower polymorphism observed in Aβ fibrils derived from brains of patients with Alzheimer's disease. We find that lauric acid stabilizes both ring-like and barrel-shaped models, with the effect being stronger for barrel-like models than for ring-like oligomers.
虽然阿尔茨海默病与患者大脑中 Aβ 纤维的存在相关,但更可能的致病因子是其前体,即可溶性低聚物,它们可能形成孔道或以其他方式扭曲细胞膜。利用全原子分子动力学模拟,我们研究了月桂酸等脂肪酸的存在如何改变由三链 Aβ 链构建的成孔低聚物的稳定性。这种变化会改变富含脂肪酸的大脑环境中淀粉样蛋白的分布,因此可以解释在阿尔茨海默病患者大脑来源的 Aβ 纤维中观察到的较低多态性。我们发现月桂酸使环状和桶状模型都更加稳定,对桶状模型的影响比对环状低聚物的影响更强。