(E/Z)-Farnesyl pyrophosphate

(E/Z)-Farnesyl pyrophosphate ((E/Z)-Farnesyl diphosphate), a 15-carbon isoprenoid, is a metabolic intermediate of the mevalonate (MVA) pathway. (E/Z)-Farnesyl pyrophosphate is a TRPM2 (TRP Channel) agonist, activates TRPM2 opening for ion influx. (E/Z)-Farnesyl pyrophosphate is a key branch substrate for cholesterol synthesis, ubiquinones synthesis, protein farnesylation decoration, and geranyl-geranyl pyrophosphate (GGPP) synthesis^[1]. In Vitro:(E/Z)-Farnesyl pyrophosphate functions as an identified danger signal to trigger acute cell death leading to neuron loss in stroke. Harboring both a hydrophobic 15-carbon isoprenyl chain and a heavily charged pyrophosphate head, (E/Z)-Farnesyl pyrophosphate leads to acute cell death independent of its downstream metabolic pathways. Mechanistically, extracellular calcium influx and the cation channel transient receptor potential melastatin 2 (TRPM2) exhibit essential roles in (E/Z)-Farnesyl pyrophosphate-induced cell death. (E/Z)-Farnesyl pyrophosphate activates TRPM2 opening for ion influx^[1]. In Vivo:In terms of a mouse model constructing by middle cerebral artery occlusion (MCAO), (E/Z)-Farnesyl pyrophosphate accumulates in the brain, which indicates the function of the (E/Z)-Farnesyl pyrophosphate and TRPM2 danger signal axis in ischemic injury. (E/Z)-Farnesyl pyrophosphate/TRPM2 signaling axis and the MVA pathway exhibit important roles in brain ischemia and potentially neurodegenerative diseases^[1].