Graduate Studies Faculty
Bruce Gold, Ph.D.
Programs:Cell & Developmental Biology
Program in Molecular & Cellular Biosciences
Research Interests:nerve regeneration neuroprotection neuroimmunophilin peripheral neuropathy multiple sclerosis, medical » Click here for more about Dr. Gold's research » PubMed Listing
Preceptor RotationsDr. Gold has not indicated availability for preceptor rotations at this time.
Faculty MentorshipDr. Gold has not indicated availability as a mentor at this time.
Summary of Current Research
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. The speed of regeneration is critical since longer delays are associated with a worse prognosis for achieving full functional recovery. This laboratory discovered 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. Two key findings reveal that the mechanism is distinct from that underlying immunosuppression (which is mediated by binding to the immunophilin FK506-binding protein-12 (FKBP-12) and subsequent calcineurin inhibition). First, the nerve regenerative and immunosuppressant properties of FK506 are separable: nonimmunosuppressant (non-calcineurin) derivatives also speed nerve regeneration. Second, studies using FKBP-12 knock-out mice reveal that the neurotrophic action of these agents does not involve FKBP-12. Instead, neurite outgrowth is mediated via binding to FKBP-52, a component of steroid receptor complexes. Subsequently, new structural classes of compounds with neurotrophic activity have been identified based upon their ability to bind to other chaperone proteins comprising steroid receptor complexes (e.g., Hsp-90). Molecular studies on this novel signaling pathway reveal the involvement of MAP kinase pathway as a down-stream mediator of FK506's neurotrophic action. Neuroimmunophilin ligands are also orally effective in enhancing axonal regeneration following spinal cord injury and in neurotoxic chemical-induced models of human neurodegenerative disease (e.g., Parkinson's disease). Recent clinical findings show that FK506 speeds nerve regeneration in humans. Components of steroid receptor complexes represent potential targets for the development of new drugs for the treatment of neurological disorders.
- Ph.D., University of Medicine and Dentistry of New Jersey, 1981