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George Yancopoulos
George D. Yancopoulos (born 1959) is a Greece, Greek-United States, American biomedical scientist who is the co-founder, president and chief scientific officer of Regeneron Pharmaceuticals. Yancopoulos is an elected member of the National Academy of Sciences, a fellow of the American Academy of Arts and Sciences (AAAS), and the holder of more than 100 patents. He is a principal inventor and developer of Regeneron's ten FDA-approved or -authorized treatments, as well as of Regeneron's foundational technologies for target and drug development, such as its proprietary TRAP technology, and the VelociGene and VelocImmune antibody technologies. Early life and education Yancopoulos is the son of Greeks, Greek immigrants, and spent his early childhood in Woodside, New York. As a student at the Bronx High School of Science, Yancopoulos was a top winner of the 1976 Westinghouse Science Talent Search. Intel and then Regeneron later assumed the title sponsorship for the Science Talent Searc ...
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Columbia University Vagelos College Of Physicians And Surgeons
The Columbia University College of Physicians and Surgeons (officially known as Columbia University Roy and Diana Vagelos College of Physicians and Surgeons) is the medical school of Columbia University, located at the Columbia University Irving Medical Center in the Washington Heights neighborhood of Manhattan. Founded in 1767 by Samuel Bard as the medical department of King's College (now Columbia University), the College of Physicians and Surgeons was the first medical school in the Thirteen Colonies to award the Doctor of Medicine (MD) degree. Beginning in 1993, the College of Physicians and Surgeons was also the first U.S. medical school to hold a white coat ceremony. Following a gift of $250 million from Roy and Diana Vagelos in 2017, the school became the first medical school in the nation to replace loans with scholarships for all students who qualify for financial aid when it did so in 2018. Columbia is affiliated with NewYork-Presbyterian Hospital. Students additi ...
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CNTF
Ciliary neurotrophic factor is a protein that in humans is encoded by the ''CNTF'' gene. The protein encoded by this gene is a polypeptide hormone and neurotrophic factor whose actions have mainly been studied in the nervous system where it promotes neurotransmitter synthesis and neurite outgrowth in certain neural populations including astrocytes. It is a hypothalamic neuropeptide that is a potent survival factor for neurons and oligodendrocytes and may be relevant in reducing tissue destruction during inflammatory attacks. A mutation in this gene, which results in aberrant splicing, leads to ciliary neurotrophic factor deficiency, but this phenotype is not causally related to neurologic disease. In addition to the predominant monocistronic transcript originating from this locus, the gene is also cotranscribed with the upstream ZFP91 gene. Cotranscription from the two loci results in a transcript that contains a complete coding region for the zinc finger protein but lacks a c ...
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Motor Neuron
A motor neuron (or motoneuron), also known as efferent neuron is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or indirectly control effector organs, mainly muscles and glands. There are two types of motor neuron – upper motor neurons and lower motor neurons. Axons from upper motor neurons synapse onto interneurons in the spinal cord and occasionally directly onto lower motor neurons. The axons from the lower motor neurons are efferent nerve fibers that carry signals from the spinal cord to the effectors. Types of lower motor neurons are alpha motor neurons, beta motor neurons, and gamma motor neurons. A single motor neuron may innervate many muscle fibres and a muscle fibre can undergo many action potentials in the time taken for a single muscle twitch. Innervation takes place at a neuromuscular junction and twitches can become superimpo ...
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Agrin
Agrin is a large proteoglycan whose best-characterised role is in the development of the neuromuscular junction during embryogenesis. Agrin is named based on its involvement in the aggregation of acetylcholine receptors during synaptogenesis. In humans, this protein is encoded by the ''AGRN'' gene. This protein has nine domains homologous to protease inhibitors. It may also have functions in other tissues and during other stages of development. It is a major proteoglycan component in the glomerular basement membrane and may play a role in the renal filtration and cell-matrix interactions. Agrin functions by activating the MuSK protein (for Muscle-Specific Kinase), which is a receptor tyrosine kinase required for the formation and maintenance of the neuromuscular junction. Agrin is required to activate MuSK. Agrin is also required for neuromuscular junction formation. Discovery Agrin was first identified by the U.J. McMahan laboratory, Stanford University. Mechani ...
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Neuromuscular Junction
A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation to function—and even just to maintain muscle tone, avoiding atrophy. In the neuromuscular system, nerves from the central nervous system and the peripheral nervous system are linked and work together with muscles. Synaptic transmission at the neuromuscular junction begins when an action potential reaches the presynaptic terminal of a motor neuron, which activates voltage-gated calcium channels to allow calcium ions to enter the neuron. Calcium ions bind to sensor proteins (synaptotagmins) on synaptic vesicles, triggering vesicle fusion with the cell membrane and subsequent neurotransmitter release from the motor neuron into the synaptic cleft. In vertebrates, motor neurons release acetylcholine (ACh), a small molecule neurotransmitter, which ...
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MuSK Protein
MuSK (for Muscle-Specific Kinase) is a receptor tyrosine kinase required for the formation and maintenance of the neuromuscular junction. It is activated by a nerve-derived proteoglycan called agrin, which is similarly also required for neuromuscular junction formation. MuSK signaling Upon activation by its ligand agrin, MuSK signals via the proteins called casein kinase 2 (CK2), Dok-7 and rapsyn, to induce "clustering" of acetylcholine receptors ( AChR). Both CK2 and Dok-7 are required for MuSK-induced formation of the neuromuscular junction, since mice lacking Dok-7 failed to form AChR clusters or neuromuscular synapses, and since downregulation of CK2 also impedes recruitment of AChR to the primary MuSK scaffold. In addition to the proteins mentioned, other proteins are then gathered, to form the endplate to the neuromuscular junction. The nerve terminates onto the endplate, forming the neuromuscular junction - a structure required to transmit nerve impulses to the muscle, a ...
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Receptor Tyrosine Kinase
Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins. Receptor tyrosine kinases have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Mutations in receptor tyrosine kinases lead to activation of a series of signalling cascades which have numerous effects on protein expression. The receptors are generally activated by dimerization and substrate presentation. Receptor tyrosine kinases are part of the larger family of protein tyrosine kinases, encompassing the receptor tyrosine kinase proteins which contain a transmembrane domain, as well as the non-receptor tyrosine kinases which do not possess transmembrane domains. History The first RTKs to be discovered were the ...
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LNGFR
The p75 neurotrophin receptor (p75NTR) was first identified in 1973 as the low-affinity nerve growth factor receptor (LNGFR) before discovery that p75NTR bound other neurotrophins equally well as nerve growth factor. p75NTR is a neurotrophic factor receptor. Neurotrophic factor receptors bind Neurotrophins including Nerve growth factor, Neurotrophin-3, Brain-derived neurotrophic factor, and Neurotrophin-4. All neurotrophins bind to p75NTR. This also includes the immature pro-neurotrophin forms. Neurotrophic factor receptors, including p75NTR, are responsible for ensuring a proper density to target ratio of developing neurons, refining broader maps in development into precise connections. p75NTR is involved in pathways that promote neuronal survival and neuronal death. Receptor family p75NTR is a member of the tumor necrosis factor receptor superfamily. p75NTR/LNGFR was the first member of this large family of receptors to be characterized, that now contains about 25 receptors, in ...
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TrkB
Tropomyosin receptor kinase B (TrkB), also known as tyrosine receptor kinase B, or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the ''NTRK2'' gene. TrkB is a receptor for brain-derived neurotrophic factor (BDNF). The standard pronunciation for this protein is "track bee". Function Tropomyosin receptor kinase B is the high affinity catalytic receptor for several "neurotrophins", which are small protein growth factors that induce the survival and differentiation of distinct cell populations. The neurotrophins that activate TrkB are: BDNF (Brain Derived Neurotrophic Factor), neurotrophin-4 (NT-4), and neurotrophin-3 (NT-3). As such, TrkB mediates the multiple effects of these neurotrophic factors, which includes neuronal differentiation and survival. Research has shown that activation of the TrkB receptor can lead to down regulation of the Chloride potassium symporter 5, KCC2 chloride transporter in ...
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Nerve Growth Factor
Nerve growth factor (NGF) is a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons. It is perhaps the prototypical growth factor, in that it was one of the first to be described. Since it was first isolated by Nobel laureates Rita Levi-Montalcini and Stanley Cohen in 1954, numerous biological processes involving NGF have been identified, two of them being the survival of pancreatic beta cells and the regulation of the immune system. Structure NGF is initially in a 7S, 130- kDa complex of 3 proteins – Alpha-NGF, Beta-NGF, and Gamma-NGF (2:1:2 ratio) when expressed. This form of NGF is also referred to as proNGF (NGF precursor). The gamma subunit of this complex acts as a serine protease, and cleaves the N-terminal of the beta subunit, thereby activating the protein into functional NGF. The term ''nerve growth factor'' usually refers to the 2.5S, 26-kDa beta subunit of the p ...
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Neurotrophic
Neurotrophic factors (NTFs) are a family of biomolecules – nearly all of which are peptides or small proteins – that support the growth, survival, and differentiation of both developing and mature neurons. Most NTFs exert their trophic effects on neurons by signaling through tyrosine kinases, usually a receptor tyrosine kinase. In the mature nervous system, they promote neuronal survival, induce synaptic plasticity, and modulate the formation of long-term memories. Neurotrophic factors also promote the initial growth and development of neurons in the central nervous system and peripheral nervous system, and they are capable of regrowing damaged neurons in test tubes and animal models. Some neurotrophic factors are also released by the target tissue in order to guide the growth of developing axons. Most neurotrophic factors belong to one of three families: (1) neurotrophins, (2) glial cell-line derived neurotrophic factor family ligands (GFLs), and (3) neuropoieti ...
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