Antimicrobial Peptide, Lumbricusin, Ameliorates Motor Dysfunction and Dopaminergic Neurodegeneration in a Mouse Model of Parkinson's Disease

J Microbiol Biotechnol. 2015 Oct;25(10):1640-7. doi: 10.4014/jmb.1507.07011.

Abstract

We recently reported that the antimicrobial peptide Lumbricusin (NH2-RNRRWCIDQQA), isolated from the earthworm, increases cell proliferation in neuroblastoma SH-SY5Y cells. Here, we investigated whether Lumbricusin has neurotropic activity in mouse neural stem cells (MNSCs) and a protective effect in a mouse model of Parkinson's disease (PD). In MNSCs isolated from mouse brains, Lumbricusin treatment significantly increased cell proliferation (up to 12%) and reduced the protein expression of p27(Kip1) through proteasomal protein degradation but not transcriptional regulation. Lumbricusin inhibited the 6-OHDA-induced apoptosis of MNSCs, and also showed neuroprotective effects in a mouse PD model, ameliorating the motor impairments seen in the pole, elevated body swing, and rotation tests. These results suggest that the Lumbricusin-induced promotion of neural cell proliferation via p27(Kip1) degradation has a protective effect in an experimental PD model. Thus, the antimicrobial peptide Lumbricusin could possibly be developed as a potential therapeutic agent for the treatment of PD.

Keywords: Antimicrobial peptide; Parkinson's disease,; cell cycle arrest; cell proliferation (neurotropine); neuroprotective activity; proteasomal protein degradation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / administration & dosage
  • Antimicrobial Cationic Peptides / metabolism*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Dopaminergic Neurons / drug effects*
  • Helminth Proteins / administration & dosage
  • Helminth Proteins / metabolism*
  • Mice
  • Motor Disorders / drug therapy*
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / physiology
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / metabolism*
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / pathology*
  • Treatment Outcome

Substances

  • Antimicrobial Cationic Peptides
  • Helminth Proteins
  • Neuroprotective Agents
  • lumbricusin peptide, Lumbricus terrestris