Oxidative stress has been implicated in the etiology of
neurodegenerative diseases and aging. Indeed, accumulation of
reactive oxygen species, such as
hydrogen peroxide, generated by inflammatory cells, leads to oxidative stress, which may contribute to the neuronal degeneration observed in a wide variety of
neurodegenerative disorders of the central nervous system, such as
Alzheimer's disease. The present study indicates that H(2)O(2)-induced cell death can be inhibited in the presence of
1,2,4-triazine derivatives, as measured by MTT and
caspase-3 activity. We further show that these compounds exert their protective effect by up-regulation of hemeoxygenase-1,
glutamylcysteine synthetase,
glutathione peroxidase and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), while they inhibit
NF-kappaB and decrease lipid peroxidation. It shows that there is a potential cross talk between
NF-kappaB and Nrf2, an important cytoprotective
transcription factor in the presence of these compounds. Moreover, in order for drugs to be effective in the treatment of
neurodegenerative diseases, they must be capable of penetrating the blood-brain barrier, whereas more than 98% of all potential
central nervous system drugs don't cross. Using a reliable model based on the artificial neural network indicated that these compounds satisfy this requirement.