Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration

Parkinson's disease (PD) is a neurodegenerative disorder of uncertain pathogenesis characterized by the loss of the nigrostriatal dopaminergic neurons, which can be modeled by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Increased expression of cyclooxygenase type 2 (COX-2) and production of prostaglandin E(2) have been implicated in neurodegeneration in several pathological settings. Here we show that COX-2, the rate-limiting enzyme in prostaglandin E(2) synthesis, is up-regulated in brain dopaminergic neurons of both PD and MPTP mice. COX-2 induction occurs through a JNKc-Jun-dependent mechanism after MPTP administration. We demonstrate that targeting COX-2 does not protect against…

• UD
  U.S. Department of Defense

  Award: DAMD 17-03-1
• PD
  Parkinson's Disease Foundation

  Award: NS38370
• MS
  Michigan State University
• DF
  Deutsche Forschungsgemeinschaft
• NI
  National Institutes of Health

  Awards: NS11766, NS38370
• CO
  College of Engineering, Michigan State University