title: Atorvastatin stimulates neuroblastoma cells to induce neurite outgrowth by increasing cellular prion protein expression.
abstract: 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 (PrP(C)) 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 PrP(C) mediates neurite outgrowth induced by HMG-CoA reductase inhibitors. Atorvastatin, a strong HMG-CoA reductase inhibitor, induced neurite outgrowth and increased PrP(C) levels in Neuro2a cells in a time- and dose-dependent manner. PrP(C) mRNA expression was also increased by atorvastatin. Farnesol, a non-sterol mevalonate derivative, attenuated the atorvastatin-induced neurite outgrowth and increase in PrP(C). Neuro2a cells overexpressing PrP(C) showed a remarkable enhancement of atorvastatin-induced neurite outgrowth compared with mock cells transfected with empty pCI-neo vector. These findings suggest that PrP(C) 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.
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. twatanabe@fukuoka-u.ac.jp
authors.forename: Takuya
authors.initials: T
authors.lastname: Watanabe
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yasutaka
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nishioku
authors.forename: Akio
authors.initials: A
authors.lastname: Nakashima
authors.forename: Koujiro
authors.initials: K
authors.lastname: Futagami
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D045744:Cell Line, Tumor; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D051379:Mice; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D009447:Neuroblastoma; D011328:Prions / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011328:Prions; D011758:Pyrroles; D000069059:Atorvastatin