Fig. 2

Prelamin A maturation process as a therapeutical target. Processing of prelamin A is a succession of enzymatic reactions that lead to a mature form of lamin A: The first step is the farnesylation of a cysteyl residue to obtain a farnesylated form of prelamin. Subsequently, a protease (ZMPSTE24 or RCE1) cleaves the aaX residues from the C-terminus tail. Finally, ZMPSTE24 protease cleaves the last 15 residues from the C-terminus to obtain mature prelamin A. In Hutchinson-Gilford Progeria Syndrome (HGPS) patient cells, the last cleavage by ZMPSTE24 does not take place leading to the abnormal accumulation of farnesylated lamin A. Potential therapeutic approaches are indicated in red: pravastatin, zoledronate, mono-aminopyrimidynes (mono-APs) and farnesyltransferase inhibitors (FTI)