PEP-1-heat shock protein 27 protects from neuronal damage in cells and in a Parkinson's disease mouse model

FEBS J. 2012 Jun;279(11):1929-42. doi: 10.1111/j.1742-4658.2012.08574.x. Epub 2012 Apr 16.

Abstract

Heat shock proteins (HSPs) are a highly conserved family of proteins that are induced in response to various environmental stressors including reactive oxygen species. HSP27 is a chaperone protein with the ability to increase cell survival in response to oxidative stress. Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons. Although the mechanism of PD remains unclear, oxidative stress is known to be important in its pathogenesis. This study investigated the protective effects of PEP-1-HSP27 on neuronal damage induced by 1-methyl-4-phenyl pyridinium (MPP(+) ) in SH-SY5Y cells and in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. PEP-1-HSP27 rapidly entered the cells and protected them against MPP(+) -induced toxicity by inhibiting the reactive oxygen species levels and DNA fragmentation. Furthermore, transduced PEP-1-HSP27 prevented dopaminergic neuronal cell death in the substantia nigra of MPTP-induced PD mouse models. These results demonstrate that PEP-1-HSP27 provides a potential strategy for therapeutic delivery against various diseases and is a potential tool for the treatment of PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / administration & dosage
  • 1-Methyl-4-phenylpyridinium / toxicity
  • Animals
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cysteamine / analogs & derivatives*
  • Cysteamine / metabolism
  • DNA Fragmentation / drug effects
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology
  • Escherichia coli
  • HSP27 Heat-Shock Proteins / genetics
  • HSP27 Heat-Shock Proteins / metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / drug therapy*
  • Parkinson Disease, Secondary / metabolism
  • Peptides / genetics
  • Peptides / metabolism*
  • Reactive Oxygen Species / antagonists & inhibitors
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / pharmacology*
  • Rotarod Performance Test
  • Substantia Nigra / drug effects*
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology

Substances

  • HSP27 Heat-Shock Proteins
  • Pep-1 peptide
  • Peptides
  • Reactive Oxygen Species
  • Recombinant Fusion Proteins
  • Cysteamine
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • 1-Methyl-4-phenylpyridinium