论文部分内容阅读
Neurotrophic factors, naturally occurring polypeptides in the nervous system that support the development and survival of neurons, were originally identified based on their ability to prevent naturally occurring cell death in the developing nervous system.They are also found to promote survival after injury or protect neurons in toxin-disease animal models.In addition to neuroprotective effects, these factors exert trophic effects on neurons, stimulating increases in neuronal metabolism, cell size, and process outgrowth.These properties underlie expectations for neuro-restoration, in which growth of new axons and synapses could lead to functional improvement in patients who are significantly disabled by disease.The neurotrophin brain-derived neurotrophic factor (BDNF) also plays a central role in synaptic plasticity and neurogenesis.Converging lines of evidence implicate BDNF in the pathophysiology of major depressive disorder (MDD).Serum BDNF levels are abnormally low in patients suffering from MDD and that the BDNF levels are elevated following a course of antidepressant treatment.Evidence from preclinical and clinical studies indicates that it may be possible to use neurotrophic factors to prevent, slow the progression of, or even reverse the effects of a number of neurodegenerative diseases, depressive disorder, or other types of CNS insults.However, neurotrophins present specific problems when used as therapeutic agents.They can be given neither orally nor intravenously, since they are not able to cross the BBB.There can be indirect and direct means of using neurotrophins as therapeutic agents.The indirect method overcomes the BBB by "activation of neurotrophin synthesis" using antidepressive agents such as specific serotonin reuptake inhibitors (SSRIs).On the other hand, the direct method of using neurotrophins as neurotherapeutics means direct intravenous administration and supplement of BBB-penetrating neurotrophins.Animal studies and the state-of-theart techniques of passage through the BBB will be reviewed in the presentation.The delivery of neurotrophic factors to the brain is one of the largest obstacles in the development of more effective therapies for depressive disorder and other neurodegenerative disorders.Therefore, any clinical usefulness of neurotrophins as a potential CNS therapy will depend on the use of a suitable carrier system that enhances its transport through the BBB.