Neurotrophic Factors
Neurotrophic factors are small proteins that exert survival-promoting and trophic (derived from the Greek meaning "to nourish") actions on neuronal (or nerve) cells. During development, these factors play a critical role in mediating the ability of a target (e.g., skeletal muscle) of a neuron (e.g., spinal cord motor neuron) to prevent the death of the nerve cell. In addition to these effects on neuronal survival, neurotrophic factors play a critical role in the "quality of life" of neurons. Neurotrophic factors regulate growth of neurons, associated metabolic functions such as protein synthesis, and the ability of the neuron to make the neurotransmitters that carry chemical signals which allow the neuron to communicate with other neurons or with other targets (muscles, glands, etc.). Because of these actions, neurotrophic factors play a significant role in the maintenance of neuronal function throughout an individual's entire lifetime.
In addition to their physiological role, neurotrophic factors can be administered exogenously (i.e., pharmacologically) as either pure proteins or via gene therapy. Administered pharmacologically, neurotrophic factors can prevent nerve cell death caused by various insults including nerve injury, brain trauma, and exposure to toxins. They can also enhance the metabolism, growth and function of neurons.
Although several proteins can be shown to exert neurotrophic factor-like actions in experimental system, two major protein families are proven "classic" neurotrophic factors in vivo (Latin for "within the living body"); loss of these factors results in neuronal death during development and/or atrophy and hypofunction in the adult. Members of these families of proteins have been shown to exert survival-promoting and trophic effects in many experimental models of nervous system injury and neurodegenerative disease.
Historically, the first growth factor family discovered was the "neurotrophins" consisting of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT 4/5). These factors act on many types of nerve cells, including sensory neurons in the periphery, cortical neurons, hippocampal neuron, and basal forebrain cholinergic nerve cells in the brain. Many of these cells are involved in memory function and are lost in Alzheimer's Disease.
A second family of factors is called the glial cell line-derived neurotrophic factor [GDNF] family ligands. There are at least four members of this family including GDNF, neurturin, artemin, and persephin. These factors also act on many important nerve cells, includings dopaminergic neurons in the substantia nigra within the brain. The death of the latter population of cells is responsible for Parkinson's disease.
Neurotrophic factors have the ability to promote nerve cell survival and to maintain and/or enhance nerve cell function. Therefore, they are attractive candidates as therapeutic agents in many clinical conditions and chronic neurodegenerative diseases such as Alzheimer's and Parkinson's disease and acute injuries including trauma and stroke.