title: Multitarget ligands and theranostics: sharpening the medicinal chemistry sword against prion diseases.
abstract: Prion diseases (PrDs) are fatal neurodegenerative disorders, for which no effective therapeutic and diagnostic tools exist. The main pathogenic event has been identified as the misfolding of a disease-associated prion protein. Nevertheless, pathogenesis seems to involve an intricate array of concomitant processes. Thus, it may be unlikely that drugs acting on single targets can effectively control PrDs. In addition, diagnosis occurs late in the disease process, by which point it is difficult to determine a successful therapeutic intervention. In this context, multitarget ligands (MTLs) and theranostic ligands (TLs) emerge for their potential to effectively cure and diagnose PrDs. In this review, we discuss the medicinal chemistry challenges of identifying novel MTLs and TLs against PrDs, and envision their impact on prion drug discovery.
authors: Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona, Spain.
authors: Salvatore
authors: S
authors: Bongarzone
authors: Matteo
authors: M
authors: Staderini
authors: Maria Laura
authors: ML
authors: Bolognesi
mesh_terms: D002626:Chemistry, Pharmaceutical; D055808:Drug Discovery; D006801:Humans; D008024:Ligands; D017096:Prion Diseases / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics
chemical_list: D008024:Ligands
keywords: Creutzfeldt–Jakob disease; bivalent ligands; prion drug discovery; protein misfolding diseases; rare diseases