Introduction of neurotrophic factors

The first neurotrophic factor found by humans was first succeeded by Italian neuroscientist Rita Levi-Montalcini and American biochemist Stanley Cohen in 1956; Cohen also unexpectedly discovered another species that promotes epidermal cell growth, proliferation and differentiation Growth factor, and thus the factor named epidermal growth factor (Epidermal Growth Factor, EGF). To this end, Levi-Montalcini and Cohen in 1986 jointly won the Nobel Prize in Physiology or Medicine.

The discovery process of neurotrophic factors can be traced back to the 1920s and 1930s. American neuroscientist Samuel Randall Detwiler and American embryologist Viktor Hamburger had discovered that neuronal innervation of target cells plays an important role in neuronal survival. They observed that the number of sensory neurons in the dorsal root ganglion of the amphibian embryos could be due to the implantation of limb buds (limb buds, protrusions that protrude from the outer limbs of the embryos in the future limb) to the target Cells and increased. In contrast, the number of neurons can be significantly reduced by removing normal target cells. They believe that the number of neurons caused by the target cells changes the target cells affect the proliferation of nerve cells and differentiation of the reflection. But in the 1940s, this interpretation was questioned by Italian young neuroscientist Rita Levi-Montalcini because in her experiments she was surprised to find that neuronal death was perfectly normal during embryonic development.

The discovery process of neurotrophic factor

In the autumn of 1947, Levi-Montalcini accepted the invitation of Professor Viktor Hamburger to the United States to participate in his work and repeated her own experiments on chicken embryos many years ago, which was an important turning point in Levi-Montalcini's life, If written. In a key experiment, she and Viktor Hamburger confirmed that the removal of chicken buds from chicken embryos would result in more sensory neuronal death compared to chicken embryos that retained intact buds.

In the development of the central nervous system, nerve cells also occurred in normal death. Hamburger later confirmed that about half of the motor neurons generated during the embryonic development of the spinal cord of the spinal cord were destined to be apoptotic. Moreover, in those experiments similar to those of the sensory ganglia, Hamburger found that the number of motor neurons deaths could be increased by removal of target cells or due to increased limb buds. So the size of the muscle target for the survival of spinal motor neurons is extremely important. The death of the neuron overproduction process occurs almost anywhere in the central nervous system and the peripheral nervous system.

The findings of Hamburger and Levi-Montalcini prompted them to suggest the neurotrophic factor, which assumes that the developing target cells of the neurons can produce and secrete a limited but essential nutrient Sexual substances or nutritional factors, and this nutritional material or nutritional factors can be taken in the nerve endings, those who can not get the right amount of neurotrophic factor neurons will apoptosis. Based on this assumption, eventually Levi-Montalcini and her colleagues at the Hamburger laboratory biochemist Stanley Cohen successfully separated from the nerve growth factor (nerve growth factor, NGF).

Classification and role of nerve growth factor

The discovery of NGF is a milestone in studying growth factors and stimulating the search for other neurotrophic factors. It is known that NGF is only one of a number of secretory factors that promote neuronal survival. One of the most studied trophic factors is neurotrophins. Four major neurotrophic factors have been isolated from mammals. They are: NGF, brain derived neurotrophic factor (BDNF), neurotrophic factor 3 (NT-3) and neurotrophic factor 4/5 (NT-4/5). In addition, there may be neurotrophic factor 6 (NT-6).

NGF is widely found in humans and animals. If the NGF antiserum into the new animals, can make almost all of the sympathetic ganglia damage; and the anti-serum into the mother can lead to fetal rat brain failure. It can be seen that NGF is necessary for the growth and survival of sympathetic neurons and sensory neurons. The experiment also showed that NGF could increase the cAMP level of basal forebrain and striatal cholinergic neurons, increase the activity of choline acetyltransferase and play an important role in the growth and survival of these neurons. Various NTs have different effects in protecting neurons and preventing apoptosis, but there are also some cross and overlapping. Removal of NT-3 gene can cause significant loss of skin touch-pressure sensory receptors; DBNF-deficient mice, the number of peripheral sensory neurons decreased, vestibular ganglia severe degeneration.

Interpretation of neurotrophic factors

1, neurotrophic factor refers to the body can promote the survival of nerve cells, growth, differentiation of a class of protein factors in the past has been that nerve growth factor in the development process to regulate neuronal survival, and no effect on adult neurons.

2, the general neurotrophic substances and the survival of nerve cells have a regulatory role in the growth factor collectively referred to as neurotrophic factors, such as NGF, BDNF, NT3, NT45 and NT6 and so on.

3, Nutritional factors These factors are also known as neurotrophic factors, they are endogenous peptide substances, can prevent apoptosis (cell death) receptor P75 and TGF-RI effect and promote neuronal growth and survival.

4, in a sense S100 protein can be called a neurotrophic factor, its increase in the post-glial glial cells, is the nerve tissue repair at the molecular level of the brain brain hemorrhage around the brain tissue GFAP and S -100 expression.

5, these substances are called neurotrophic factors including nerve growth factor (nevergrowthfactorNGF) brain-derived neurotrophic factor (brainderivedneurotrophicfactorBDNF) neurotrophin-3 (NT-3) neurotrophic factor-45 (NT-45).