Research conducted in this laboratory focuses on the characterization of molecular events involved in transduction of biologic signals generated by interaction of neurotrophic factors with their cognate receptors, as well as regulation of neurotrophic factor expression. Neurotrophins represent a family of peptides that have been demonstrated to be critical for the survival and development of neurons that comprise the central and peripheral nervous systems. Presently, use of neurotrophins as therapeutic factors is receiving considerable attention, partic- ularly with regard to the potential treatment of devastating diseases such as Alzheimer's, Parkinson's, Huntington's and ALS. Understanding, as completetly as possible, biochemical processes responsible for mediating intracellular signals involved in regulation of neurotrophic factor expression and release could lead to the discovery of suitable molecules that are able traverse the blood-brain barrier and elicit biologically relevent increases in levels of neurotrophic factor. There is a continuing trend to develop neurotrophic factors as biologics for the treatment of severely compromising neurodegenerative diseases. In addition to serving as a primary treatment modality, neurotrophic factors are being considered for use as adjunctive therapies to ameliorate peripheral neuropathy adverse events, as support for the implantation of precursor neuronal cells, and as components of implanted neurologic devices. Without exception, neurotrophic factors currently under development for treatment of central nervous system disorders must be delivered directly into the brain due to exclusion capabilities of the blood-brain barrier. In spite of advances in understanding of the specificity and mechanisms of neurotrophic factor biologic activity, the requisite for central administration of recombinant neurotrophic factor molecules remains a major impediment. To facilitate the effective review of neurotrophic factor as potential products it is essential to maintain a core of neurobiology expertise within the center that is familiar with aspects concerning regulation of neurotrophic factor expression and function.
