THE THERAPEUTIC POTENTIALS OF NEUROTROPHIC FACTORS FOR DISEASES OF THE NERVOUS-SYSTEM

Neurotrophic factors are secreted proteins that regulate the long-term survival and differentiation of neurones in the peripheral and centra l nervous systems (PNS and CNS). Their profound effects on the structu ral integrity of the nervous system have led to intense interest in th e potential use of the factors as therapeutic agents for neurodegenera tive diseases. In the present review, we summarise the current data on the physiological role of these proteins based on in vitro investigat ions and animal models, and discuss their clinical potential as therap eutic agents in the treatment of neurological disorders. A rationale f or neurotrophic factor therapy can be built for a specific neurologica l disease once a particular neurotrophic factor is identified to regul ate vulnerable neurones in the affected areas. Progress has been made in the use of neurotrophic factors as an alternative therapy to conven tional drug treatment, particularly for Alzheimer's disease, Parkinson 's disease and peripheral neuropathy. Production of chimeric neurotrop hins may combine the beneficial aspects of a number of neurotrophic fa ctors. Delivery of exogenous protein factors to the CNS remains one of the major obstacles for trophic factor therapy. Second generation app roaches (including transplantation of genetically engineered cells, di rect gene transfer into the brain and pharmacological manipulation of the levels of endogenous neurotrophic factors) may prove to be effecti ve in overcoming the technical problems surrounding direct CNS deliver y. The discovery of new trophic molecules and development of novel del ivery methods represent two important aspects of neurotrophic therapy for neurodegenerative diseases.