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Apoptosis Inducing Factor and PARP‐Mediated Injury in the MPTP Mouse Model of Parkinson's Disease
Author(s) -
WANG HONGMIN,
SHIMOJI MIKA,
YU SEONGWOON,
DAWSON TED M.,
DAWSON VALINA L.
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2003.tb07471.x
Subject(s) - mptp , pars compacta , substantia nigra , excitotoxicity , neurotoxin , programmed cell death , parkin , dopaminergic , poly adp ribose polymerase , microbiology and biotechnology , apoptosis inducing factor , neurotoxicity , biology , neuroprotection , mitochondrion , glutamate receptor , chemistry , apoptosis , parkinson's disease , dopamine , pharmacology , neuroscience , caspase , biochemistry , receptor , medicine , toxicity , polymerase , disease , pathology , enzyme , organic chemistry
A bstract : 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.

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