Bruce D. Gold

Ph.D., University of Medicine and Dentistry of New Jersey, 1981

Center for Research on Occupational and Environmental Toxicology

Adjunct Associate Professor, Cell and Developmental Biology

Neuronal (axonal) degeneration is produced by mechanical injury (as in Carpal Tunnel Syndrome), following exposure to variety of occupational and environmental chemicals, and by metabolic and inheritable factors. Recovery of function is dependent upon regeneration of injured axons which is a slow process. My laboratory was the first to discover that the systemic administration of the immunosuppressant drug FK506 dose-dependently accelerates functional recovery by increasing the rate of nerve regeneration following a peripheral nerve injury in rats. The development of nonimmunosuppressant orally efficacious derivatives that enhance nerve regenerative demonstrated that these two properties are separable. These compounds also increase axonal regeneration following spinal cord injury and in neurotoxic chemical-induced models of human neurodegenerative disease (e.g., Parkinson's disease). In regard to their potential clinical use, FK506 has been recently found to speed nerve regeneration in humans. Cell cultures are used to examine the underlying mechanism by which these compounds increase nerve regeneration. Results from these studies reveal that neurite outgrowth is mediated via binding to a unique FK506-binding protein, FKBP-52, which is a component of steroid receptor complexes. Further studies implicate the involvement of the MAP kinase pathway as a down-stream mediator of FK506's neurotrophic action. Components of steroid receptor complexes (e.g., FKBP-52 and Hsp-90) represent potential targets for the development of new drugs for the treatment.Gold, B.G., Yew, J.Y., and Zeleny-Pooley, M. (1998) The immunosuppressant FK506 increases GAP-43 mRNA levels in axotomized sensory neurons. Neurosci. Letters 241:25-28.

Navarro X., Udina E., Ceballos D. and Gold B.G. (2001) Effects of FK506 on nerve regeneration and reinnervation after graft or tube repair of long nerve gaps. Muscle & Nerve 24:905-915..

Gold B.G. (2000) Neuroimmunophilin ligands and the role of steroid hormone chaperone proteins in nerve regeneration. In: B.G. Gold, G. Fischer, T. Herdegen (eds.) Immunophilins in the Brain. FKBP-ligands: Novel stratagies for the treatment of neurodegenerative disorders. Prous Science, Barcelona, Spain, 2000, pp. 3-22.

Wang M.-S. and Gold B.G. (1999) FK506 increases the regeneration of spinal cord axons in a predegenerated peripheral nerve autograft. J. Spinal Cord Medicine 22:287-296.

Gold B.G., Densmore V., Shou W., Martin M.M. and Gordon H.S. (1999) The immunophilin FK506-Binding Protein 52 (not FKBP 12) mediates the neurotrophic action of FK506. J. Pharmacol. Exp. Therap. 289:1202-1210..

To contact Dr. Gold directly: gold@ohsu.edu