Unraveling the role of peptidyl-prolyl isomerases in neurodegeneration.

Immunophilins are a family of highly conserved proteins with a peptidyl-prolyl isomerase activity that binds immunosuppressive drugs such as FK506, cyclosporin A, and rapamycin. Immunophilins can be divided into two subfamilies, the cyclophilins, and the FK506 binding proteins (FKBPs). Next to the immunophilins, a third group of peptidyl-prolyl isomerases exist, the parvulins, which do not influence the immune system. The beneficial role of immunophilin ligands in neurodegenerative disease models has been known for more than a decade but remains largely unexplained in terms of molecular mechanisms. In this review, we summarize reported effects of parvulins, immunophilins, and their ligands in the context of neurodegeneration. We focus on the role of FKBP12 in Parkinson's disease and propose it as a novel drug target for therapy of Parkinson's disease.