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KCC2
Potassium-chloride transporter member 5 (aka: KCC2 and SLC12A5) is a neuron-specific chloride potassium symporter responsible for establishing the chloride ion gradient in neurons through the maintenance of low intracellular chloride concentrations. It is a critical mediator of synaptic inhibition, cellular protection against excitotoxicity and may also act as a modulator of neuroplasticity. Potassium-chloride transporter member 5 is also known by the names: KCC2 (potassium chloride cotransporter 2) for its ionic substrates, and SLC12A5 for its genetic origin from the ''SLC12A5'' gene in humans. Animals with reduced expression of this transporter exhibit severe motor deficits, epileptiform activity, and spasticity. KCC2 knockout animals, in which KCC2 is completely absent, die postnatally due to respiratory failure. Location KCC2 is a neuron-specific membrane protein expressed throughout the central nervous system, including the hippocampus, hypothalamus, brainstem, and moto ...
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SLC12A5
Potassium-chloride transporter member 5 (aka: KCC2 and SLC12A5) is a neuron-specific chloride potassium symporter responsible for establishing the chloride ion gradient in neurons through the maintenance of low intracellular chloride concentrations. It is a critical mediator of inhibitory postsynaptic potential, synaptic inhibition, cellular protection against excitotoxicity and may also act as a modulator of neuroplasticity. Potassium-chloride transporter member 5 is also known by the names: KCC2 (potassium chloride cotransporter 2) for its ionic substrates, and SLC12A5 for its genetic origin from the ''SLC12A5'' gene in humans. Animals with reduced expression of this transporter exhibit severe motor deficits, epileptiform activity, and spasticity. KCC2 knockout mouse, knockout animals, in which KCC2 is completely absent, die postnatally due to respiratory failure. Location KCC2 is a neuron-specific membrane protein expressed throughout the central nervous system, including the ...
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TrkB Receptor
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 KCC2 chloride transporter in cells of the CNS. In addition ...
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Chloride Potassium Symporter
The chloride potassium symporter is a membrane transport protein of the solute carrier family 12 that is present in the S3-segment of the renal proximal tubule Page 780 and in the neuron. It functions in renal chloride reabsorption to transport chloride across the basolateral membrane. Chloride potassium symporter can lower intracellular chloride concentrations below the electrochemical equilibrium potential. The concentrations of K+ and Cl− ions are high inside the cell due to the activities of Na+/K+ ATPase and NKCC cotransporter, respectively. Hence, their net driving force acting on the K/Cl cotransporter favours the exit of both K+ and Cl− from the cell. Types Chloride potassium symporter are classified into: * Chloride potassium symporter 4, predominating in the kidney. * Chloride potassium symporter 5, predominating in neurons. Each is encoded by a separate gene of the solute carrier family 12, hence accounting for the numbers succeeding its name. For example, chlori ...
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WNK1
WNK (lysine deficient protein kinase 1), also known as WNK1, is an enzyme that is encoded by the ''WNK1'' gene. WNK1 is serine-threonine protein kinase and part of the "with no lysine/K" kinase WNK family. The predominant role of WNK1 is the regulation of cation-Cl− cotransporters (CCCs) such as the sodium chloride cotransporter ( NCC), basolateral Na-K-Cl symporter ( NKCC1), and potassium chloride cotransporter (KCC1) located within the kidney. CCCs mediate ion homeostasis and modulate blood pressure by transporting ions in and out of the cell. ''WNK1'' mutations as a result have been implicated in blood pressure disorders/diseases; a prime example being familial hyperkalemic hypertension (FHHt). Structure The WNK1 protein is composed of 2382 amino acids (molecular weight 230 kDa). The protein contains a kinase domain located within its short N-terminaldomain and a long C-terminal tail. The kinase domain has some similarity to the MEKK protein kinase family. As a member of ...
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WNK3
Serine/threonine-protein kinase WNK3, also known as protein kinase lysine-deficient 3, is a protein that in humans is encoded by the ''WNK3'' gene. Function WNK3 is a protein belonging to the 'with no lysine' family of serine-threonine protein kinases. These family members lack the catalytic lysine in subdomain II, and instead have a conserved lysine in subdomain I. This family member functions as a positive regulator of the transcellular Ca2+ transport pathway, and it plays a role in the increase of cell survival in a caspase 3 Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the ''CASP3'' gene. ''CASP3'' orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are als ... dependent pathway. References Further reading * * * * * * * * * * * * * * * * * * * * EC 2.7.11 {{gene-X-stub ...
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Knockout Mouse
A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or " knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are important animal models for studying the role of genes which have been sequenced but whose functions have not been determined. By causing a specific gene to be inactive in the mouse, and observing any differences from normal behaviour or physiology, researchers can infer its probable function. Mice are currently the laboratory animal species most closely related to humans for which the knockout technique can easily be applied. They are widely used in knockout experiments, especially those investigating genetic questions that relate to human physiology. Gene knockout in rats is much harder and has only been possible since 2003. The first recorded knockout mouse was created by Mario R. Capecchi, Martin Evans, and Oliver Smithies in 1989, fo ...
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Depolarization
In biology, depolarization or hypopolarization is a change within a cell (biology), cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is essential to the function of many cells, communication between cells, and the overall physiology of an organism. Most cells in higher organisms maintain an internal environment that is negatively charged relative to the cell's exterior. This difference in charge is called the cell's membrane potential. In the process of depolarization, the negative internal charge of the cell temporarily becomes more positive (less negative). This shift from a negative to a more positive membrane potential occurs during several processes, including an action potential. During an action potential, the depolarization is so large that the potential difference across the cell membrane briefly reverses polarity, with the inside of the cell becoming p ...
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Excitotoxicity
In excitotoxicity, neuron, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamic acid, glutamate become pathologically high, resulting in excessive stimulation of cell surface receptor, receptors. For example, when glutamate receptors such as the NMDA receptor or AMPA receptor encounter excessive levels of the excitatory neurotransmitter, glutamate, significant neuronal damage might ensue. Different mechanisms might lead to increased extracellular glutamate concentrations, e.g. reduced uptake by glutamate transporters (EAATs), synaptic hyperactivity, or abnormal release from different neural cell types. Excess glutamate allows high levels of calcium in biology, calcium ions (Ca2+) to enter the cell (biology), cell. Ca2+ influx into cells activates a number of enzymes, including phospholipases, endonucleases, and proteases such as calpain. These enzymes go on to damage cell structures such as components of the cytoskel ...
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Neurotrophin-4
Neurotrophin-4 (NT-4), also known as neurotrophin-5 (NT-5), is a protein that in humans is encoded by the ''NTF4'' gene. It is a neurotrophic factor that signals predominantly through the TrkB 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 kinas .... NT-4 was first discovered and isolated from xenopus and viper in the year 1991 by Finn Hallbook ''et.al'' See also * Tropomyosin receptor kinase B § Agonists References Further reading * * * * * * * * * * * * * * * * * * * External links * * Neurotrophic factors Peptide hormones Growth factors Developmental neuroscience Proteins TrkB agonists {{gene-19-stub ...
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BDNF
Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the canonical nerve growth factor (NGF), a family which also includes NT-3 and NT-4/NT-5. Neurotrophic factors are found in the brain and the periphery. BDNF was first isolated from a pig brain in 1982 by Yves-Alain Barde and Hans Thoenen. BDNF activates the TrkB tyrosine kinase receptor. Function BDNF acts on certain neurons of the central nervous system and the peripheral nervous system expressing TrkB, helping to support survival of existing neurons, and encouraging growth and Cellular differentiation, differentiation of new neurons and synapses. In the brain it is active in the hippocampus, Cerebral cortex, cortex, and basal forebrain areas vital to learning, memory, and higher thinking. BDNF is also expressed in the retina, kidneys, pros ...
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Neuroplasticity
Neuroplasticity, also known as neural plasticity or just plasticity, is the ability of neural networks in the brain to change through neurogenesis, growth and reorganization. Neuroplasticity refers to the brain's ability to reorganize and rewire its neural connections, enabling it to adapt and function in ways that differ from its prior state. This process can occur in response to learning new skills, experiencing environmental changes, recovering from injuries, or adapting to sensory or cognitive deficits. Such adaptability highlights the dynamic and ever-evolving nature of the brain, even into adulthood. These changes range from individual neuron pathways making new connections, to systematic adjustments like cortical remapping or neural oscillation. Other forms of neuroplasticity include homologous area adaptation, cross modal reassignment, map expansion, and compensatory masquerade. Examples of neuroplasticity include neural circuit, circuit and network changes that result fr ...
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Colon Cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel movements, weight loss, abdominal pain and fatigue. Most colorectal cancers are due to lifestyle factors and genetic disorders. Risk factors include diet, obesity, smoking, and lack of physical activity. Dietary factors that increase the risk include red meat, processed meat, and alcohol. Another risk factor is inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis. Some of the inherited genetic disorders that can cause colorectal cancer include familial adenomatous polyposis and hereditary non-polyposis colon cancer; however, these represent less than 5% of cases. It typically starts as a benign tumor, often in the form of a polyp, which over time becomes cancerous. Colorectal cancer may be diagnosed by ...
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