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

**Authors:** Guangyu Shi, Yikao Hu, Xiaolin Bai, Xun Liao

PMC · DOI: 10.3390/molecules30091952 · Molecules · 2025-04-28

## TL;DR

This study identifies two earthworm peptides that protect nerve cells and improve symptoms in models of Parkinson’s disease.

## Contribution

The discovery of novel neuroprotective peptides from earthworms with potential for Parkinson’s disease treatment.

## Key findings

- Two peptides improved cell viability in a Parkinson’s disease cell model by enhancing mitochondrial function.
- The peptides upregulated PINK1 and Parkin mRNAs and showed PINK1 agonistic activity in vitro.
- The peptides improved lifespan and motor function in a Parkinson’s disease fly model.

## Abstract

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 PINK1B9 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.

## Linked entities

- **Genes:** PINK1 (PTEN induced kinase 1) [NCBI Gene 65018], park (parkin) [NCBI Gene 40336]
- **Chemicals:** MPP+ (PubChem CID 39484), ATP (PubChem CID 5957), dopamine (PubChem CID 681)
- **Diseases:** Parkinson’s disease (MONDO:0005180)
- **Species:** Lumbricus terrestris (taxon 6398)

## Full-text entities

- **Genes:** PRKN (parkin RBR E3 ubiquitin protein ligase) [NCBI Gene 5071] {aka AR-JP, LPRS2, PARK2, PDJ}, PINK1 (PTEN induced kinase 1) [NCBI Gene 65018] {aka BRPK, PARK6}
- **Diseases:** neurodegenerative (MESH:D019636), neuroblastoma (MESH:D009447), PD (MESH:D010300)
- **Species:** Metaphire sieboldi (earthworm, species) [taxon 506672], Lumbricus terrestris (common earthworm, species) [taxon 6398], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** SH-SY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12074337/full.md

## References

35 references — full list in the complete paper: https://tomesphere.com/paper/PMC12074337/full.md

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Source: https://tomesphere.com/paper/PMC12074337