Journal
JOURNAL OF NEUROSCIENCE
Volume 25, Issue 28, Pages 6594-6600Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0970-05.2005
Keywords
MPTP; Parkinson's disease; oxidative stress; inflammation; neuroprotection; nitrotyrosine
Categories
Funding
- NIA NIH HHS [R01 AG021191, AG021191] Funding Source: Medline
- NIEHS NIH HHS [P30ES07033, P30 ES007033] Funding Source: Medline
- NINDS NIH HHS [NS38586, NS42269, NS38370, P01 NS011766, R01 NS038586, R01 NS042269, P50 NS038370, NS11766-27A2] Funding Source: Medline
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Parkinson's disease (PD) is characterized by a loss of ventral midbrain dopaminergic neurons, which can be modeled by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ( MPTP). Inflammatory oxidants have emerged as key contributors to PD- and MPTP-related neurodegeneration. Here, we show that myeloperoxidase (MPO), a key oxidant-producing enzyme during inflammation, is upregulated in the ventral midbrain of human PD and MPTP mice. We also show that ventral midbrain dopaminergic neurons of mutant mice deficient in MPO are more resistant to MPTP-induced cytotoxicity than their wild-type littermates. Supporting the oxidative damaging role of MPO in this PD model are the demonstrations that MPO-specific biomarkers 3-chlorotyrosine and hypochlorous acid-modified proteins increase in the brains of MPTP-injected mice. This study demonstrates that MPO participates in the MPTP neurotoxic process and suggests that inhibitors of MPO may provide a protective benefit in PD.
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