Protein farnesylation is upregulated in Alzheimer’s human brains and neuron-specific suppression of farnesyltransferase mitigates pathogenic processes in Alzheimer’s model mice

摘要

The mevalonate/isoprenoid and protein prenylation pathways. Farnesyl pyrophosphate (FPP) is derived from mevalonate, serving as the branching point for the non-steroid isoprenoid pathway and the sterol synthesis pathway. FPP and geranylgeranyl pyrophosphate (GGPP) are used for protein farnesylation and geranylgeranylation (collectively called protein prenylation) by the catalytic actions of farnesyltransferase (FT) and geranylgeranyl transferases (GGTs), respectively. HMG-CoA: 3-Hydroxy-3-methylglutaryl-CoA, HMGCR: Hydroxymethylglutaryl-CoA reductase, GPPS: Geranyl pyrophosphate synthase, FPPS: Farnesyl pyrophosphate synthase, GGPPS: Geranylgeranyl pyrophosphate synthase, FT: Farnesyltransferase, GGT: Geranylgeranyltransferase-1/2