PEP-1-p18 prevents neuronal cell death by inhibiting oxidative stress and Bax expression

P18, a member of the INK4 family of cyclin-dependent kinaseinhibitors, is a tumor suppressor protein and plays a key cellsurvival role in a variety of human cancers. Under pathophysiologicalconditions, the INK4 group proteins participate in novelbiological functions associated with neuronal diseases andoxidative stress. Parkinson’s disease (PD) is characterized by loss ofdopaminergic neurons, and oxidative stress is important in itspathogenesis. Therefore, we examined the effects of PEP-1-p18 onoxidative stress-induced SH-SY5Y cells and in a PD mouse model.The transduced PEP-1-p18 markedly inhibited 1-methyl-4-phenylpyridinium-induced SH-SY5Y cell death by inhibiting Baxexpression levels and DNA fragmentation. Additionally, PEP-1-p18prevented dopaminergic neuronal cell death in the substantia nigraof a 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine-induced PDmouse model. These results indicate that PEP-1-p18 may be auseful therapeutic agent against various diseases and is a potentialtool for treating PD.