Poly(ADP-ribose)polymerase inhibitor can attenuate the neuronal death after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice.
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.
Yokoyama
Hironori
H
Department of Neurobiology and Therapeutics, Graduate School and Faculty of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.
Kuroiwa
Hayato
H
Tsukada
Tatsuya
T
Uchida
Hiroto
H
Kato
Hiroyuki
H
Araki
Tsutomu
T
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors; D000818:Animals; D001549:Benzamides / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology; D009457:Neuroglia / Q000187:drug effects / Q000201:enzymology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D009498:Neurotoxins / Q000037:antagonists & inhibitors; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D016896:Treatment Outcome
D001549:Benzamides; D004791:Enzyme Inhibitors; D009498:Neurotoxins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C037689:benzamide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases