Shi Guangyu, Hu Yikao, Bai Xiaolin, Liao Xun
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Molecules. 2025 Apr 28;30(9):1952. doi: 10.3390/molecules30091952.
The aim of this study was to identify peptides from with neuroprotective effects. Two peptides (GYSFTTTAER and AVFPSIVGR) isolated from earthworms improved cell viability of the SH-SY5Y human neuroblastoma cell line treated with 1-methyl-4-phenyl-1,2,3-tetrahydropyridinehydrochloride (MPP), a commonly used model of Parkinson's disease (PD). Both peptides increased the mitochondrial membrane potential and upregulated the mRNAs of mitophagy regulators PINK1 and Parkin in the MPP-damaged cells. The in vitro assay and molecular docking indicated that both peptides exhibited moderate PINK1 agonistic activity. Furthermore, GYSFTTTAER and AVFPSIVGR extended the lifespan, improved locomotor behavior, and raised the ATP and dopamine levels at all ages in mutant flies, a PD model characterized by loss-of-function of PINK1. These findings suggest that earthworm-derived peptides possess anti-neurodegenerative properties and hold potential for the development of health products and therapeutic agents for PD.
本研究的目的是从蚯蚓中鉴定出具有神经保护作用的肽。从蚯蚓中分离出的两种肽（GYSFTTTAER和AVFPSIVGR）提高了用1-甲基-4-苯基-1,2,3-四氢吡啶盐酸盐（MPP）处理的SH-SY5Y人神经母细胞瘤细胞系的细胞活力，MPP是帕金森病（PD）常用的模型。两种肽均增加了线粒体膜电位，并上调了MPP损伤细胞中自噬调节因子PINK1和Parkin的mRNA。体外试验和分子对接表明，两种肽均表现出适度的PINK1激动活性。此外，GYSFTTTAER和AVFPSIVGR延长了PINK1功能丧失特征的PD模型——突变果蝇在所有年龄段的寿命，改善了运动行为，并提高了ATP和多巴胺水平。这些发现表明，蚯蚓衍生的肽具有抗神经退行性特性，在开发用于PD的健康产品和治疗剂方面具有潜力。
