Simvastatin-mediated enhancement of long-term potentiation is driven by farnesyl-pyrophosphate depletion and inhibition of farnesylation

Article ID	Journal	Published Year	Pages	File Type
6275823	Neuroscience	2012	9 Pages	PDF

Abstract

â¶Simvastatin (SV) enhances hippocampal LTP via inhibition of isoprenoid production. â¶Levels of farnesyl-PP but not geranylgeranyl-PP affect hippocampal LTP. â¶Inhibiting farnesyl transferase (FTase) mimics the LTP-enhancing property of SV. â¶FTase inhibition increases the activation of PI3-K/Akt during LTP induction. â¶These data suggest that SV enhances LTP by modulating pathways downstream of FTase.

Keywords

geranylgeranyl transferase inhibitor GGTI N-methyl d-aspartate GGPP FTi HMG-CoA PI3-K HFS NMDA FTase GGTase Geranylgeranylpyrophosphate PPF FPP MEV aCSF Mevalonate 3-hydroxy-3-methylglutaryl coenzyme A fEPSPs Akt Statins Isoprenoids Alzheimer's disease high-frequency stimulation paired-pulse facilitation long-term potentiation LTP Simvastatin farnesyl pyrophosphate farnesyl transferase Phosphatidylinositol 3-kinase artificial cerebral spinal fluid Farnesyl transferase inhibitor Hippocampus veh Vehicle field excitatory postsynaptic potentials protein kinase B Protein prenylation Synaptic plasticity geranylgeranyl transferase