title: [Immunophilin ligands: from immunosuppressants to neuroprotective drugs].
abstract: Non-immunosuppressive immunophilin ligands (NI-IPLs) are attracting attention as new candidate drugs for neuroprotection and/or neurorestoration, particularly since they do not have the adverse effects of immunosuppressants. However, it is not yet enough to understand that NI-IPLs are useful drugs for treating neurological disorders. In particular, the molecular mechanism of NI-IPL activity in target cells in the brain remains obscure. In this review, we focused on the molecular basis of the neuroprotective properties of IPLs. Our findings suggest that IPLs have neuroprotective effects mediated by multiple beneficial properties such as a glutathione (GSH)-activating effect, a neurotrophic factor (NTF)-activating effect, and an anti-apoptotic effect, but not by an immunosuppressive effect, both in cell cultures and in vivo. In particular, the GSH-activating effect and the NTF-activating effect of NI-IPLs may be essential to the expression of their neuroprotective properties. Thus, NI-IPLs might have a potentially beneficial effect by ameliorating neurological disorders, since they do not cause serious side effects such as immune deficiency.
authors.affiliation: Department of Clinical Pharmacy, Shujitsu University School of Pharmacy, Okayama, 703-8516 Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Norio
authors.initials: N
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D020104:Immunophilins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000378:metabolism; D008024:Ligands; D009414:Nerve Growth Factors / Q000378:metabolism; D009422:Nervous System Diseases / Q000188:drug therapy; D018696:Neuroprotective Agents; D016559:Tacrolimus / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D008024:Ligands; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D016572:Cyclosporine; D020104:Immunophilins; D005978:Glutathione; D016559:Tacrolimus