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

P18, a member of the INK4 family of cyclin-dependent kinase inhibitors, is a tumor suppressor protein and plays a key cell survival role in a variety of human cancers. Under pathophysiological conditions, the INK4 group proteins participate in novel biological functions associated with neuronal diseases and oxidative stress. Parkinson`s disease (PD) is characterized by loss of dopaminergic neurons, and oxidative stress is important in its pathogenesis. Therefore, we examined the effects of PEP-1-p18 on oxidative stress-induced SH-SY5Y cells and in a PD mouse model. The transduced PEP-1-p18 markedly inhibited 1-methyl-4-phenyl pyridinium-induced SH-SY5Y cell death by inhibiting Bax expression levels and DNA fragmentation. Additionally, PEP-1-p18 prevented dopaminergic neuronal cell death in the substantia nigra of a 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine-induced PD mouse model. These results indicate that PEP-1-p18 may be a useful therapeutic agent against various diseases and is a potential tool for treating PD. [BMB Reports 2012; 45(9): 532-537]