Abstract
An excessive expression of poly(ADP-ribose)polymerase (PARP) has been demonstrated to play a key role in the pathogenesis of Parkinson's disease (PD). Here we investigated the therapeutic effect of the PARP inhibitor benzamide against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice. In our HPLC and Western blot analysis, pretreatment with benzamide showed a neuroprotective effect against MPTP neurotoxicity in mice. Posttreatment with benzamide also attenuated MPTP neurotoxicity in mice. Furthermore, our immunohistochemical study showed that posttreatment with benzamide significantly prevented neuronal damage by suppressing overexpression of neuronal, microglial, and astroglial PARP after MPTP treatment. These findings have important implications for the therapeutic time window and choice of PARP inhibitors in PD patients. Our present findings provide further evidence that PARP inhibitor may offer a novel therapeutic strategy for PD.
(c) 2009 Wiley-Liss, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / antagonists & inhibitors
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Animals
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Benzamides / pharmacology*
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Benzamides / therapeutic use
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Brain / drug effects
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Brain / enzymology
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Brain / physiopathology
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Disease Models, Animal
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Enzyme Inhibitors / pharmacology
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Enzyme Inhibitors / therapeutic use
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Male
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Mice
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Mice, Inbred C57BL
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Nerve Degeneration / drug therapy*
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Nerve Degeneration / enzymology*
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Nerve Degeneration / physiopathology
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Neuroglia / drug effects
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Neuroglia / enzymology
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Neurons / drug effects
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Neurons / enzymology
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Neurotoxins / antagonists & inhibitors
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Parkinsonian Disorders / drug therapy*
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Parkinsonian Disorders / enzymology*
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Parkinsonian Disorders / physiopathology
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerase Inhibitors*
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Poly(ADP-ribose) Polymerases / metabolism
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Treatment Outcome
Substances
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Benzamides
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Enzyme Inhibitors
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Neurotoxins
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Poly(ADP-ribose) Polymerase Inhibitors
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benzamide
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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Parp1 protein, mouse
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerases