神经营养因子和神经生长和修复

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Stanley Cohen
Rita Levi-Montalcini
1986: Levi-Montalcini and Cohen split the Nobel prize for Physiology or Medicine
“for their discovery of growth factors”
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Effect of Removing or Augmenting Neural Targets on the Survival of R ePlNa2te3d09N2.JePuGrons
1939: Victor Hamburger showed that transplantation of a supernumerary limb resulted in increased numbers of sensory and motor neurons in the spinal cord.
brain (shares ~50% homolog with NGF)
NT-3 and NT-4/5: were obtained by PCR cloning
All these factors are synthesized as ~250 aa precursors that are processed into 120 aa proteins
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But now that thinking has been turned upside down. Scientists recently have discovered a whole family of proteins called neurotrophic factors. These proteins play a crucial role in the development and survival of nerve cells, or neurons, and in supporting adult neurons to keep them healthy throughout life.
Hamburger, V. and Levi-Montalcini, R. (1949) J. Exp. Zool. 111: 457-502.
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1954: neurite outgrowth assay
1960: NGF purified
– extract
1969: NGF purified to homwenku.baidu.comgeneity
Autophoshorylation results in further activation of the kinase domain, leading to activation of three potential signaling
Neurotrophic factors and Their receptors
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For decades, scientists believed that brain cells of the central nervous system could not regrow following damage due to trauma such as head injury or disorders such as Alzheimer's disease. Treatments did not exist. The outlook was bleak.
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Neurotrophins BDNF (brain derived neurotrophic factor) on cortical neurons
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Trk receptor signaling
When a neurotrophin binds to a trk receptor, the kinase domain is activated resulting in autophosphorylation.
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The neurotrophic factor hypothesis
1934: Victor Hamburger discovered that removal of a limb bud resulted in reduced numbers of sensory and motor neurons in the spinal cord.
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The main List of Neurotrophic Factors
NGF: sympathetic neurons and some sensory
neurons (CNS neurons do not require NGF for survival)
BDNF: NGF-related factor purified in 1982 from pig
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The neurotrophic factor hypothesis
Based on his limb-bud experiments, V. Hamburger hypothesized that the targets of innervating neurons provide signals that recruit undifferentiated cells to develop into sensory or motor neurons.
(he was wrong) In 1942, Levi-Montalcini and Levi proposed that target derived signals maintain survival of differentiating neurons. In 1949, Hamburger and Levi-Montalcini repeated the limb bud experiments and found that their results supported the neurotrophic hypothesis.