College of Food Science and Engineering, Bohai University, Jinzhou 121013, P.R. China.
Food Funct. 2020 Jul 1;11(7):6643-6651. doi: 10.1039/d0fo00971g. Epub 2020 Jul 13.
Acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta-secretase 1 (BACE 1) play vital roles in the development and progression of Alzheimer's disease (AD). The objective of the present study was to identify fish roe-derived anti-AD peptides with activities against AChE, BChE, and BACE 1. Fish roe proteins were cleaved in silico by gastrointestinal proteases, and the released peptides were collected. Subsequently, the toxicity, solubility, and biological properties of these novel di- and tri-peptides were predicted and validated. Finally, potential anti-AD peptides were docked to targets, i.e., AChE, BChE, and BACE 1. A novel anti-AD tripeptide WIR with potent inhibition of AChE and BACE 1 was identified, with IC values of 43.32 ± 1.22 μM and 2.27 ± 0.35 mM, respectively. In addition, the inhibition rate of WIR (at a concentration of 1.06 ± 0.87 μM) against BChE was 33.5%, and the peptide WIR was able to simultaneously interact with AChE, BChE, and BACE 1. Residues Ser286 of AChE, Asp70 of BChE, and Thr231, Arg235 of BACE 1 played key roles in the interaction with peptide WIR. In summary, peptide WIR exhibits the potential to be an effective treatment for AD.
乙酰胆碱酯酶（AChE）、丁酰胆碱酯酶（BChE）和β-分泌酶 1（BACE 1）在阿尔茨海默病（AD）的发展和进展中发挥着重要作用。本研究的目的是鉴定具有抑制 AChE、BChE 和 BACE 1 活性的鱼卵来源的抗 AD 肽。通过胃肠道蛋白酶对鱼卵蛋白进行计算机模拟切割，并收集释放的肽。随后，预测和验证了这些新型二肽和三肽的毒性、溶解性和生物学特性。最后，将潜在的抗 AD 肽对接至靶标，即 AChE、BChE 和 BACE 1。鉴定出一种新型抗 AD 三肽 WIR，对 AChE 和 BACE 1 的抑制作用较强，IC 值分别为 43.32±1.22 μM 和 2.27±0.35 mM。此外，WIR（在 1.06±0.87 μM 浓度下）对 BChE 的抑制率为 33.5%，肽 WIR 能够同时与 AChE、BChE 和 BACE 1 相互作用。AChE 的 Ser286 残基、BChE 的 Asp70 残基和 BACE 1 的 Thr231、Arg235 残基在与肽 WIR 的相互作用中发挥关键作用。总之，肽 WIR 具有成为 AD 有效治疗方法的潜力。
