• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress.

Mutations of the DJ-1 (PARK7) gene are linked to familial Parkinson's disease. We used gene targeting to generate DJ-1-deficient mice that were viable, fertile, and showed no gross anatomical or neuronal abnormalities. Dopaminergic neuron numbers in the substantia nigra and fiber densities and dopamine levels in the striatum were normal. However, DJ-1-/- mice showed hypolocomotion when subjected to amphetamine challenge and increased striatal denervation and dopaminergic neuron loss induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine. DJ-1-/-embryonic cortical neurons showed increased sensitivity to oxidative, but not nonoxidative, insults. Restoration of DJ-1 expression to DJ-1-/- mice or cells via adenoviral vector delivery mitigated all phenotypes. WT mice that received adenoviral delivery of DJ-1 resisted 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine-induced striatal damage, and neurons overexpressing DJ-1 were protected from oxidative stress in vitro. Thus, DJ-1 protects against neuronal oxidative stress, and loss of DJ-1 may lead to Parkinson's disease by conferring hypersensitivity to dopaminergic insults.

Pubmed ID: 15784737

Authors

  • Kim RH
  • Smith PD
  • Aleyasin H
  • Hayley S
  • Mount MP
  • Pownall S
  • Wakeham A
  • You-Ten AJ
  • Kalia SK
  • Horne P
  • Westaway D
  • Lozano AM
  • Anisman H
  • Park DS
  • Mak TW

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

April 5, 2005

Associated Grants

None

Mesh Terms

  • Animals
  • Base Sequence
  • Cell Death
  • Corpus Striatum
  • DNA, Complementary
  • Denervation
  • Gene Targeting
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • MPTP Poisoning
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity
  • Neurons
  • Oncogene Proteins
  • Oxidative Stress
  • Parkinson Disease
  • Parkinsonian Disorders