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 central nervous systems (PNS and CNS). Their profound effects on the structural integrity of the nervous system have led to intense interest in the potential use of the factors as therapeutic agents for neurodegenerative diseases. In the present review, we summarise the current data on the physiological role of these proteins based on in vitro investigations and animal models, and discuss their clinical potential as therapeutic agents in the treatment of neurological disorders. A rationale for neurotrophic factor therapy can be built for a specific neurological disease once a particular neurotrophic factor is identified to regulate vulnerable neurones in the affected areas. Progress has been made in the use of neurotrophic factors as an alternative therapy to conventional drug treatment, particularly for Alzheimer's disease, Parkinson's disease and peripheral neuropathy. Production of chimeric neurotrophins may combine the beneficial aspects of a number of neurotrophic factors. Delivery of exogenous protein factors to the CNS remains one of the major obstacles for trophic factor therapy. Second generation approaches (including transplantation of genetically engineered cells, direct gene transfer into the brain and pharmacological manipulation of the levels of endogenous neurotrophic factors) may prove to be effective in overcoming the technical problems surrounding direct CNS delivery. The discovery of new trophic molecules and development of novel delivery methods represent two important aspects of neurotrophic therapy for neurodegenerative diseases.