PARK7 DJ-1 protects against degeneration of nigral dopaminergic neurons in Parkinson's disease rat model

Neurobiol Dis. 2006 Oct;24(1):144-58. doi: 10.1016/j.nbd.2006.06.004. Epub 2006 Jul 24.

Abstract

DJ-1 has recently been shown to be responsible for onset of familial Parkinson's disease (PD), PARK7. DJ-1 has been shown to play roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to trigger onset of PD. In this study, a recombinant DJ-1 protein was administrated into the brain of PD model rats that had been injected to 6-hydroxydopamine (6-OHDA) in the left substantia nigra. PD phenotypes, including dopaminergic neuron death in the substantia nigra, decrease in dopamine, and dopamine transporter levels in the striatum, and motor abnormality, were dramatically improved by wild-type DJ-1 but not L166P DJ-1, a mutant form of DJ-1 found in PD patients. Furthermore, production of reactive oxygen species and cell death induced by 6-OHDA in SH-SY5Y cells and mesencephalic neurons were inhibited by addition of the recombinant DJ-1. These findings suggest that DJ-1 is a therapeutic target for PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking / pharmacology
  • Behavior, Animal / drug effects
  • Cell Death / drug effects
  • Cells, Cultured
  • Dopamine / metabolism
  • Dopamine / physiology*
  • Dopamine Agents / pharmacology
  • Glutathione / chemistry
  • Intracellular Signaling Peptides and Proteins / administration & dosage
  • Intracellular Signaling Peptides and Proteins / pharmacology*
  • Male
  • Microinjections
  • Neostriatum / metabolism
  • Nerve Degeneration / genetics*
  • Nerve Degeneration / pathology*
  • Neurons / drug effects
  • Neurons / physiology
  • Neuroprotective Agents*
  • Oncogene Proteins / administration & dosage
  • Oncogene Proteins / pharmacology*
  • Oxidative Stress / physiology
  • Oxidopamine
  • Parkinson Disease / genetics*
  • Parkinson Disease / pathology*
  • Protein Deglycase DJ-1
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • Substantia Nigra / physiology*
  • Sympatholytics

Substances

  • Antibodies, Blocking
  • Dopamine Agents
  • Intracellular Signaling Peptides and Proteins
  • Neuroprotective Agents
  • Oncogene Proteins
  • Reactive Oxygen Species
  • Recombinant Proteins
  • Sympatholytics
  • Oxidopamine
  • PARK7 protein, human
  • Protein Deglycase DJ-1
  • Glutathione
  • Dopamine