Neurodegenerative disorders are CNS diseases characterized by synaptic loss, neuronal atrophy, and death as common pathol. hallmarks.Parkinson's disease (PD) is one of the most common neurol. disorders, affecting over 6.3 million people globally, and 1.5 million people in North America.Parkinson's disease (PD) belongs to a group of conditions called motor system disorders, which are the result of the loss of dopamine-producing neurons in the substantia nigra.A hallmark of PD neuronal degeneration is aberrant aggregation of alpha-synuclein (α-SYN).In PD, the protein is present in a fibrillar, aggregated form inside cytoplasmic inclusions called Lewy bodies.Enzymes of the FK506 binding protein (FKBP) family accelerate the aggregation of recombinant α-SYN in vitro and FK506, a specific FKBP inhibitor, abrogates this effect.FKBPs are members of the immunophilin family of proteins.These proteins are enzymes with peptidyl-prolyl cis-trans isomerase (PPIase) activity and bind to immunosuppressants such as FK506.PPIase enzymes catalyze cis-trans isomerization of X-Pro peptide bonds, an essential and rate-limiting step in the process of protein folding.The human FKBP family contains 15 principal members with many different functions.Among these, four members, namely, FKBP12, FKBP38, FKBP52, and FKBP65, are enriched in the human brain.Importantly, numerous clin. and pre-clin. studies have demonstrated that two FKPBs, FKBP12 and FKPB52, are involved in PD pathol.The results of this new series of FKBP 12 and FKBP-52 inhibitors will be presented.