Hong Zhou, Shengtang Liu, Qiwen Shao, Dongfang Ma, Zaixing Yang and Ruhong Zhou
Abstract
Docosahexaenoic acid (DHA) is one of the omega-3 polyunsaturated fatty acids, which has shown promising applications in lowering Aβ peptide neurotoxicity in vitro by preventing aggregation of Aβ peptides and relieving accumulation of Aβ fibrils. Unfortunately, the underlying molecular mechani**s of how DHA interferes with the aggregation of Aβ peptides remain largely enigmatic. Herein, ggregation behaviors of amyloid-β(Aβ)16-21 peptides (KLVFFA) with or without the presence of a HA molecule were comparatively studied using extensive all-atom molecular dynamics simulations. e found that DHA could effectively suppress the aggregation of KLVFFA peptides by redirecting eptides to unstructured oligomers. The highly hydrophobic and flexible nature of DHA made it randomly ut tightly entangled with Leu-17, Phe-19, and Phe-20 residues to form unstructured but stable omplexes. These lower-ordered unstructured oligomers could eventually pass through energy barriers to form ordered β-sheet structures through large conformational fluctuations. This study depicts a microscopic picture for understanding the role and mechani** of DHA in inhibition of aggregation of Aβ peptides, which is generally believed as one of the important pathogenic mechani**s of Alzheimer’s disease.