The PTEN inhibitor bpV(pic) promotes neuroprotection against amyloid ß-peptide (25-35)-induced oxidative stress and neurotoxicity.

ABSTRACT

OBJECTIVES: The aim of this study was to elucidate the mechanism underlying the neuroprotective effects of the phosphatase and tensin homolog (PTEN) inhibitor, bisperoxovanadium-pic [bpV(pic)]. METHODS: We determined the effects of bpV(pic) on amyloid-ß-peptide-(25-35)-induced neurotoxicity, particularly intracellular reactive oxygen species (ROS) production and mitochondria-mediated apoptotic signaling, in a human neuroblastoma (SH-SY5Y) cell model. RESULTS: We found that exposure of SH-SY5Y cells to amyloid ß peptides (Aß25-35) resulted in a significant reduction in cell viability accompanied by increased lactate dehydrogenase (LDH) release, elevated levels of intracellular ROS, and decreased superoxide dismutase (SOD) activities, all of which were reversed by co-treatment with bpV(pic). Moreover, bpV(pic) induced significant protection against Aß25-35-induced apoptosis, and effectively suppressed mitochondria-dependent apoptotic signaling triggered by Aß25-35. DISCUSSION: Aß peptides are thought to cause neurodegeneration in Alzheimer's disease (AD), via the induction of free radical oxidative stress. Our results indicate that bpV(pic) provides protection against Aß25-35-induced oxidative stress and neurotoxicity, suggesting that bpV(pic) could be a potential therapeutic candidate in the treatment of neurodegenerative diseases such as AD.