Key Laboratory of Cold Chain Logistics Technology for Agricultural Products (Ministry of Agriculture and Rural Affairs), Institute of Agricultural Products Processing and Nuclear Technology, Hubei, Academy of Agricultural Sciences, Wuhan 430064, China.
Key Laboratory of Cold Chain Logistics Technology for Agricultural Products (Ministry of Agriculture and Rural Affairs), Institute of Agricultural Products Processing and Nuclear Technology, Hubei, Academy of Agricultural Sciences, Wuhan 430064, China; School of Life and Health Sciences, Hubei University of Technology, Wuhan 430000, China.
Food Chem. 2024 Dec 15;461:140834. doi: 10.1016/j.foodchem.2024.140834. Epub 2024 Aug 12.
Providing antioxidants and targeting acetylcholinesterase (AChE) are key strategies in treating neurocognitive dysfunction. In this study, bioactive sturgeon (Acipenser schrenckii) spinal cord peptides (SSCPs) with antioxidant and AChE inhibitory potency were extracted and separated from sturgeon spinal cord by enzymatic hydrolysis and ultrafiltration, and targeted peptide PGGW was screened via computer simulated molecular docking. Further, the molecular dynamic interactions of the PGGW with superoxide dismutase (SOD) and AChE were analyzed, and the protective effect of PGGW on glutamate-induced PC12 cells in vitro was evaluated. The <3 kDa fraction of SSCPs displays the most potent antioxidative efficacy (1 mg/mL, DPPH•: 89.07%, ABTS: 76.35%). Molecular dynamics simulation showed that PGGW was stable within AChE and tightly bound to residues SER203, PHE295, ILE294 and TRP236. When combined with SOD, the indole group of PGGW was stuck inside SOD, but the tail chain PGG fluctuated greatly outside. Surface plasmon resonance demonstrated that PGGW has a high binding affinity for AChE (KD = 1.4 mM) and 0.01 mg/mL PGGW provided good protection against glutamate-induced apoptosis. The findings suggest a promising strategy for drug research on neurodegenerative diseases.
提供抗氧化剂和靶向乙酰胆碱酯酶 (AChE) 是治疗神经认知功能障碍的关键策略。在这项研究中，通过酶解和超滤从鲟鱼脊髓中提取和分离出具有抗氧化和 AChE 抑制活性的生物活性鲟鱼脊髓肽 (SSCPs)，并通过计算机模拟分子对接筛选出靶向肽 PGGW。进一步分析了 PGGW 与超氧化物歧化酶 (SOD) 和 AChE 的分子动态相互作用，并评估了 PGGW 对体外谷氨酸诱导的 PC12 细胞的保护作用。SSCPs 的 <3 kDa 部分显示出最强的抗氧化功效（1 mg/mL，DPPH•：89.07%，ABTS：76.35%）。分子动力学模拟表明，PGGW 在 AChE 内稳定，并与残基 SER203、PHE295、ILE294 和 TRP236 紧密结合。当与 SOD 结合时，PGGW 的吲哚基团卡在 SOD 内，但尾部 PGG 在外部剧烈波动。表面等离子体共振表明，PGGW 对 AChE 具有高结合亲和力（KD = 1.4 mM），0.01 mg/mL PGGW 对谷氨酸诱导的细胞凋亡有很好的保护作用。研究结果为神经退行性疾病的药物研究提供了一种有前途的策略。
