PolyADP-ribosylation can, in turn, modify the activities of various proteins. PAW has been shown to be activated by nicks in the DNA molecule and to be involved in DNA plasticity-related phenomena such as DNA repair, carcinogenesis, cell proliferation and gene expression. PARP inhibitors, such as benzamide, have been shown to differently affect the long-term survival of different cell types subjected to varying insults. For example, benzamide can increase the mortality of glucocorticoid-treated mouse lymphoma cells, while it can also prevent the death of a murine macrophage tumor cell line exposed to hydrogen peroxidation. The first part of the present series of studies was undertaken to investigate the possible involvement of PARP in glutamate-induced neurotoxicity in cerebellar granule cells in vitro, and the effects of PAW inhibitors on the survival of these neurons. In the second part of the study, the in vivo effects of PARP inhibitors on MPTP-induced catecholamine neurotoxicity in C57B1/6N mice were examined. Although these compounds might act at other sites in addition to PAW, the results of our studies indicate that PARP inhibitors possess neuroprotective potential in vivo and suggest a role of PARP in MPTP neurotoxicity.
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