Ann N Y Acad Sci 2003,
PMID: 12846982
Wang, Hongmin; Shimoji, Mika; Yu, Seong-Woon; Dawson, Ted M; Dawson, Valina L
Experimental intoxication models are used to study the more common sporadic form of Parkinson's disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP) animal models of PD provide a valuable and predictive tool to probe the molecular mechanisms of dopamine neuronal cell death in PD. MPTP is a powerful neurotoxin that induces neuronal degeneration in the substantia nigra pars compacta and produces PD-like symptoms in several mammalian species tested, a feat not yet accomplished in genetically engineered mice expressing human genetic mutations. The mechanisms of MPTP-induced neurotoxicity are not yet fully understood but involve activation of N-methyl-D-aspartate (NMDA) receptors by glutamate, production of NO by nNOS and iNOS, oxidative injury to DNA, and activation of the DNA damage-sensing enzyme poly (ADP-ribose) polymerase (PARP). Recent experiments indicate that translocation of a mitochondrial protein apoptosis inducing factor (AIF) from mitochondria to the nucleus depends on PARP activation and plays an important role in excitotoxicity-induced cell death. This article briefly reviews the experimental findings regarding excitotoxicity, PARP activation, and AIF translocation in MPTP toxicity and dopaminergic neuronal cell death.
Diseases/Pathways annotated by Medline MESH: Disease Models, Animal, MPTP Poisoning
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Text Mining Data
PARP → nNOS: "
The mechanisms of MPTP induced neurotoxicity are not yet fully understood but involve activation of N-methyl-D-aspartate ( NMDA ) receptors by glutamate, production of NO by
nNOS and iNOS, oxidative injury to DNA, and
activation of the DNA damage sensing enzyme poly ( ADP-ribose ) polymerase (
PARP )
"
PARP → iNOS: "
The mechanisms of MPTP induced neurotoxicity are not yet fully understood but involve activation of N-methyl-D-aspartate ( NMDA ) receptors by glutamate, production of NO by nNOS and iNOS , oxidative injury to DNA, and activation of the DNA damage sensing enzyme poly ( ADP-ribose ) polymerase ( PARP )
"
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