Neuroprotective effects of overexpressed cyclophilin B against Aβ-induced neurotoxicity in PC12 cells

Accumulated amyloid-beta (A beta) is a well-known cause of neuronal apoptosis in Alzheimer disease and functions in part by generating oxidative stress. Our previous work suggested that cyclophilin B (CypB) protects against endoplasmic reticulum (ER) stress. Therefore, in this study we examined the ability of CypB to protect against A beta toxicity. CypB is present in the neurons of rat and mouse brains, and treating neural cells with A beta(25-35) mediates apoptotic cell death. A beta(25-35)-induced neuronal toxicity was inhibited by the overexpression of CypB as measured by cell viability, apoptotic morphology, sub-G1 cell population, intracellular reactive oxygen species accumulation, activated caspase-3, PARP cleavage, Bcl-2 proteins, mitogen-activated protein kinase (MAPK) activation, and phosphoinositide 3-kinase (PI-3-K) activation. CypB/R95A PPlase mutants did not reduce A beta(25-35) toxicity. We showed that A beta(25-35)-induced apoptosis is more severe in a CypB knockdown model, confirming that CypB protects against A beta(25-35)-induced toxicity. Consequently, these findings suggest that CypB may protect against A beta toxicity by its antioxidant properties, by regulating MAPK and PI-3-K signaling, and through the ER stress pathway. (C) 2011 Elsevier Inc. All rights reserved.