Effector Caspase
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Effector Caspase
Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cysteine protease activity – a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. As of 2009, there are 12 confirmed caspases in humans and 10 in mice, carrying out a variety of cellular functions. The role of these enzymes in programmed cell death was first identified in 1993, with their functions in apoptosis well characterised. This is a form of programmed cell death, occurring widely during development, and throughout life to maintain cell homeostasis. Activation of caspases ensures that the cellular components are degraded in a controlled manner, carrying out cell death with minimal effect on surrounding tissues. Caspases have other identified roles in programmed cel ...
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Protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. They do this by cleaving the peptide bonds within proteins by hydrolysis, a reaction where water breaks bonds. Proteases are involved in many biological functions, including digestion of ingested proteins, protein catabolism (breakdown of old proteins), and cell signaling. In the absence of functional accelerants, proteolysis would be very slow, taking hundreds of years. Proteases can be found in all forms of life and viruses. They have independently evolved multiple times, and different classes of protease can perform the same reaction by completely different catalytic mechanisms. Hierarchy of proteases Based on catalytic residue Proteases can be classified into seven broad groups: * Serine protease ...
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Neural Development
The development of the nervous system, or neural development (neurodevelopment), refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The field of neural development draws on both neuroscience and developmental biology to describe and provide insight into the cellular and molecular mechanisms by which complex nervous systems develop, from nematodes and fruit flies to mammals. Defects in neural development can lead to malformations such as holoprosencephaly, and a wide variety of neurological disorders including limb paresis and paralysis, balance and vision disorders, and seizures, and in humans other disorders such as Rett syndrome, Down syndrome and intellectual disability. Overview of vertebrate brain development The vertebrate central nervous system (CNS) is derived from the ectoderm—the outermost germ layer of the embryo. A part of the dorsal ectoderm becomes speci ...
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Caspase 1
Caspase-1/Interleukin-1 converting enzyme (ICE) is an evolutionarily conserved enzyme that proteolytically cleaves other proteins, such as the precursors of the inflammatory cytokines interleukin 1β and interleukin 18 as well as the pyroptosis inducer Gasdermin D, into active mature peptides. It plays a central role in cell immunity as an inflammatory response initiator. Once activated through formation of an inflammasome complex, it initiates a proinflammatory response through the cleavage and thus activation of the two inflammatory cytokines, interleukin 1β (IL-1β) and interleukin 18 (IL-18) as well as pyroptosis, a programmed lytic cell death pathway, through cleavage of Gasdermin D. The two inflammatory cytokines activated by Caspase-1 are excreted from the cell to further induce the inflammatory response in neighboring cells. Cellular expression Caspase-1 is evolutionarily conserved in many eukaryotes of the Kingdom Animalia. Due to its role in the inflammatory immune ...
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Caspase 7
Caspase-7, apoptosis-related cysteine peptidase, also known as CASP7, is a human protein encoded by the ''CASP7'' gene. ''CASP7'' orthologs have been identified in nearly all mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. Function Caspase-7 is a member of the caspase (cysteine aspartate protease) family of proteins, and has been shown to be an executioner protein of apoptosis. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing by upstream caspases (caspase-8, -9) at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme in the form of a heterotetramer. The precursor of this caspase is cleaved by caspase 3, caspase 10, and caspase 9. It is activated upon cell death stimuli and induces apoptosis. Alternative splicing re ...
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Caspase 6
Caspase-6 is an enzyme that in humans is encoded by the ''CASP6'' gene. ''CASP6'' orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. Caspase-6 has known functions in apoptosis, early immune response and neurodegeneration in Huntington's and Alzheimer's disease. Function This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation cascade. Caspase 6 can also undergo self-processing without other members ...
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Science (journal)
''Science'', also widely referred to as ''Science Magazine'', is the peer-reviewed academic journal of the American Association for the Advancement of Science (AAAS) and one of the world's top academic journals. It was first published in 1880, is currently circulated weekly and has a subscriber base of around 130,000. Because institutional subscriptions and online access serve a larger audience, its estimated readership is over 400,000 people. ''Science'' is based in Washington, D.C., United States, with a second office in Cambridge, UK. Contents The major focus of the journal is publishing important original scientific research and research reviews, but ''Science'' also publishes science-related news, opinions on science policy and other matters of interest to scientists and others who are concerned with the wide implications of science and technology. Unlike most scientific journals, which focus on a specific field, ''Science'' and its rival ''Nature (journal), Nature'' c ...
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Caspase 10
Caspase-10 is an enzyme that, in humans, is encoded by the ''CASP10'' gene. This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. Mutations in this gene are associated with apoptosis defects seen in type II autoimmune lymphoproliferative syndrome. Three alternatively spliced transcript variants encoding different isoforms have been described for this gene. Interactions Caspase 10 has been shown to interact with FADD, CFLAR, Caspase 8, Fas receptor, RYBP, TNFRSF1A and TNFRSF10B. See also * The Proteolysis Map * Caspase References Further reading * ...
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Caspase 9
Caspase-9 is an enzyme that in humans is encoded by the CASP9 gene. It is an initiator caspase, critical to the apoptotic pathway found in many tissues. Caspase-9 homologs have been identified in all mammals for which they are known to exist, such as ''Mus musculus'' and ''Pan troglodytes''. Caspase-9 belongs to a family of caspases, cysteine-aspartic proteases involved in apoptosis and cytokine signalling. Apoptotic signals cause the release of cytochrome c from mitochondria and activation of apaf-1 (apoptosome), which then cleaves the pro-enzyme of caspase-9 into the active dimer form. Regulation of this enzyme occurs through phosphorylation by an allosteric inhibitor, inhibiting dimerization and inducing a conformational change. Correct caspase-9 function is required for apoptosis, leading to the normal development of the central nervous system. Caspase-9 has multiple additional cellular functions that are independent of its role in apoptosis. Nonapoptotic roles of caspase ...
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Caspase 8
Caspase-8 is a caspase protein, encoded by the ''CASP8'' gene. It most likely acts upon caspase-3. ''CASP8'' orthologs have been identified in numerous mammals for which complete genome data are available. These unique orthologs are also present in birds. Function The ''CASP8'' gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD. This protein ...
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Caspase 2
Caspase 2 also known as CASP2 is an enzyme that, in humans, is encoded by the ''CASP2'' gene. ''CASP2'' orthologs have been identified in nearly all mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. Function Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. The proteolytic cleavage of this protein is induced by a variety of apoptotic stimuli. Caspase 2 proteolytically cleaves other proteins. It belongs to a family of cysteine proteases called caspases that cleave proteins only at an amino acid following an aspartic acid residue. Within this family, caspase 2 is part of the Ich-1 subfamily. It is one of the most conserved caspases in different species of anim ...
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Autoimmune Diseases
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly any body part can be involved. Common symptoms can be diverse and transient, ranging from mild to severe, and generally include low grade fever and feeling tired. The cause is unknown. Some autoimmune diseases such as lupus run in families, and certain cases may be triggered by infections or other environmental factors. Some common diseases that are generally considered autoimmune include celiac disease, diabetes mellitus type 1, graves' disease, inflammatory bowel disease, multiple sclerosis, alopecia areata, addison’s disease, pernicious anemia, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus. The diagnosis can be difficult to determine. Treatment depends on the type and severity of the condition. Nonsteroidal ant ...
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Alzheimer's Disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term memory, remembering recent events. As the disease advances, symptoms can include primary progressive aphasia, problems with language, Orientation (mental), disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and challenging behaviour, behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years. The cause of Alzheimer's disease is poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an alle ...
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