Isolation and Characterization of Earthworm Peptides with Neuroprotective Effects in Parkinson's Disease Models

The aim of this study was to identify peptides from Lumbricus terrestris 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 PINK1 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.