Design of ligands with a high affinity to PrPC.

Abstract

Prion diseases, also known as transmissible spongiform encephalopathies (TSE), are fatal neurodegenerative disorders of the central nervous system. The main molecular mechanism underlining TSE is based on the aberrant misfolding of the cellular form of the prion protein (PrPC) into its pathological counterpart denominated PrPSc. To date there are no identified therapies. One therapeutic strategy against this disease is focused on the stabilization of the PrPC in order to prevent its conversion to PrPSc . Designing ligands targeting PrPC with a high binding affinity might augment its stability and prevent its misfolding. Here, we have set-up a computational protocol aiming at addressing this issue