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Poly(ADP‐ribose)polymerase inhibitor can attenuate the neuronal death after 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced neurotoxicity in mice
Author(s) -
Yokoyama Hironori,
Kuroiwa Hayato,
Tsukada Tatsuya,
Uchida Hiroto,
Kato Hiroyuki,
Araki Tsutomu
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22310
Subject(s) - neurotoxicity , poly adp ribose polymerase , benzamide , mptp , pharmacology , western blot , neuroprotection , parp inhibitor , chemistry , toxicity , polymerase , biology , medicine , parkinson's disease , biochemistry , disease , enzyme , stereochemistry , organic chemistry , gene
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. © 2009 Wiley‐Liss, Inc.