Neuroregenerative and neuroprotective actions of neuroimmunophilin compounds in traumatic and inflammatory neuropathies.
FK506 (tacrolimus, Prograf is an immunosuppressant drug that also has profound neuroregenerative and neuroprotective actions independent of its immunosuppressant activity. The separation of these properties has led to the development of non-immunosuppressant derivatives that retain the neurotrophic activity. This review focuses on the peripheral nerve actions of these compounds following mechanical injury (nerve crush or transection with graft repair) and in models of inflammatory neuropathies. Whereas FK506 may be indicative for the treatment of inflammatory neuropathies where its immunosuppressive action would be advantageous, non-immunosuppressant derivatives represent a new class of potential therapeutic agents for the treatment of human neurological conditions in general. Moreover, these studies have led to the discovery of a novel mechanism whereby these compounds activate intrinsic neuroregenerative and neuroprotective pathways in the neuron.
Gold
Bruce G
BG
Center for Research on Occupational and Environmental Toxicology (CROET), Oregon Health & Science University, Portland, OR 97201-3098, USA. gold@ohsu.edu
Udina
Esther
E
Bourdette
Dennis
D
Navarro
Xavier
X
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D020104:Immunophilins / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology; D008959:Models, Neurological; D009409:Nerve Crush / Q000379:methods; D009410:Nerve Degeneration / Q000209:etiology / Q000517:prevention & control*; D009416:Nerve Regeneration / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000517:prevention & control* / Q000601:surgery; D016559:Tacrolimus / Q000737:chemistry / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects
D018696:Neuroprotective Agents; D020104:Immunophilins; D016559:Tacrolimus