FKBP Ligands as Novel Therapeutics for Neurological Disorders

C.      Christner; T.      Herdegen; G.      Fischer

Abstract

Given their clinical importance for the treatment of acute and chronic neurodegenerative diseases in humans including nerve injuries (e.g. Alzheimers disease, Parkinsons disease, diabetic neuropathy) a number of different approaches were pursued to obtain selectively acting FK506-binding protein (FKBP) ligands: computational methods and target-oriented screening of natural compound and synthetic product libraries. The resulting monofunctional ligands, which inhibit the peptidyl prolyl cis / trans isomerase activity of FKBPs, highlight the role of these enzymes in neuronal signaling. The exploration of the mechanisms of neuroregenerative and neuroprotective action of some of these compounds is the main focus of ongoing neuropharmaceutical research.

Keywords: FKBP Ligands, Neurological Disorders, diabetic neuropathy, Immunosuppressant inhibitors, Rapamycin, Cyclophilin, neurogenic agents, PPIase Inhibitors