Atorvastatin stimulates neuroblastoma cells to induce neurite outgrowth by increasing cellular prion protein expression

摘要

Recently, 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors were reported to induce neurite outgrowth in vitro. However, the mechanism underlying this effect remains unclear. Cellular prion protein (PrPC) is a ubiquitous glycoprotein present on the surfaces of various cells, including neurons, and is suggested to be involved in neurite outgrowth. Therefore, the present study aimed to determine whether PrPC mediates neurite outgrowth induced by HMG-CoA reductase inhibitors. Atorvastatin, a strong HMG-CoA reductase inhibitor, induced neurite outgrowth and increased PrPC levels in Neuro2a cells in a time- and dose-dependent manner. PrPC mRNA expression was also increased by atorvastatin. Farnesol, a non-sterol mevalonate derivative, attenuated the atorvastatin-induced neurite outgrowth and increase in PrPC. Neuro2a cells overexpressing PrPC showed a remarkable enhancement of atorvastatin-induced neurite outgrowth compared with mock cells transfected with empty pCI-neo vector. These findings suggest that PrPC contributes, at least in part, to atorvastatin-induced neurite outgrowth. This phenomenon may be included among the mechanisms underlying decreased risk of Alzheimer's disease in patients treated with HMG-CoA reductase inhibitors.