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TRPM2
Transient receptor potential cation channel, subfamily M, member 2, also known as TRPM2, is a protein that in humans is encoded by the ''TRPM2'' gene. Structure The protein encoded by this gene is a non-selective calcium-permeable cation channel and is part of the Transient Receptor Potential ion channel super family. The closest relative is the cold and menthol activated TRPM8 ion channel. While TRPM2 is not cold sensitive it is activated by heat. The TRPM2 ion channel is activated by free intracellular ADP-ribose in synergy with free intracellular calcium. ADP-Ribose is produced to by the enzyme PARP in response to oxidative stress and confers susceptibility to cell death. Several alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. Function The ''TRPM2'' gene is highly expressed in the brain and was implicated by both genetic linkage studies in families and then by case control or trio allelic association stu ...
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Transient Receptor Potential
Transient receptor potential channels (TRP channels) are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC ( "C" for canonical), TRPV ("V" for vanilloid), TRPVL ("VL" for vanilloid-like), TRPM ("M" for melastatin), TRPS ("S" for soromelastatin), TRPN ("N" for no mechanoreceptor potential C), and TRPA ("A" for ankyrin). Group 2 consists of TRPP ("P" for polycystic) and TRPML ("ML" for mucolipin). Other less-well categorized TRP channels exist, including yeast channels and a number of Group 1 and Group 2 channels present in non-animals. Many of these channels mediate a variety of sensations such as pain, temperature, different kinds of tastes, pressure, and vision. In the body, some TRP channels are thought to behave like microscopic thermometers and used in animals to sense hot or cold. Some TRP channels are activated by molecules found in spices like garlic (alli ...
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ADP-ribose
Adenosine diphosphate ribose (ADPR) is an ester molecule formed into chains by the enzyme poly ADP ribose polymerase. ADPR is created from cyclic ADP-ribose (cADPR) by the CD38 enzyme using nicotinamide adenine dinucleotide (NAD+) as a cofactor. ADPR binds to and activates the TRPM2 ion channel. ADPR is the most potent agonist of the TRPM2 channel. cADPR also binds to TPRM2, and the action of both molecules is synergistic, with both molecules enhancing the action of the other molecule in activating the TRPM2 channel. See also * Adenosine diphosphate * ADP-ribosylation * Ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally-occurring form, , is a component of the ribonucleotides from which RNA is built, and so this compou ... References Nucleotides Organophosphates NADH dehydrogenase inhibitors Phosphate esters {{biochemistry-stub ...
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TRPM
TRPM is a family of transient receptor potential ion channels (''M'' standing for '' wikt:melastatin''). Functional TRPM channels are believed to form tetramers. The TRPM family consists of eight different channels, TRPM1–TRPM8. Unlike the TRPC and TRPV sub-families, TRPM subunits do not contain N-terminal ankyrin repeat motifs but, rather, contain entire functional proteins in their C-termini. TRPM6 and TRPM7, for example, contain functional α-kinase segments, which are a type of serine/threonine-specific protein kinase. Permeability and activation The relative permeability of calcium and magnesium varies widely among TRPM channels. *TRPM4 and TRPM5 are impermeable to calcium. * TRPM3, TRPM6 and TRPM7 are highly permeable to both calcium and magnesium. The mechanism of activation also varies greatly among TRPM channels. *TRPM2 is activated by ADP-ribose adenosine 5'-diphosphoribose and functions as a sensor of redox status in cells. *TRPM4 and TRPM5 are activated by intrace ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid ...
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TNF-alpha
Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homologous TNF domain. As an adipokine, TNF promotes insulin resistance, and is associated with obesity-induced type 2 diabetes. As a cytokine, TNF is used by the immune system for cell signaling. If macrophages (certain white blood cells) detect an infection, they release TNF to alert other immune system cells as part of an inflammatory response. TNF signaling occurs through two receptors: TNFR1 and TNFR2. TNFR1 is constituitively expressed on most cell types, whereas TNFR2 is restricted primarily to endothelial, epithelial, and subsets of immune cells. TNFR1 signaling tends to be pro-inflammatory and apoptotic, whereas TNFR2 signaling is anti-inflammatory and promotes cell proliferation. Suppression of TNFR1 signaling has been important for ...
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Ion Channels
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophoric proteins, the other being ion transporters. The study of ion channels often involves biophysics, electrophysiology, and pharmacology, while using techniques including voltage clamp, patch clamp, immunohistochemistry, X-ray crystallography, fluoroscopy, and RT-PCR. Their classification as molecules is referred to as channelomics. Basic features There are two distinctive features of ion channels that differentiate them from other types of ion transporter proteins: #The rate of ion transport through t ...
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Neuroblastoma
Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the abdomen, neck, or chest, or a painless bluish lump under the skin. Typically, neuroblastoma occurs due to a genetic mutation occurring during early development. Rarely, it may be due to a mutation inherited from a person's parents. Environmental factors have not been found to be involved. Diagnosis is based on a tissue biopsy. Occasionally, it may be found in a baby by ultrasound during pregnancy. At diagnosis, the cancer has usually already spread. The cancer is divided into low-, intermediate-, and high-risk groups based on a child's age, cancer stage, and what the cancer looks like. Treatment and outcomes depends on the risk group a person is in. Treatments may include observation, surgery, radiation, chemotherapy, or stem cell ...
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Molecules
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and biochemistry, the distinction from ions is dropped and ''molecule'' is often used when referring to polyatomic ions. A molecule may be homonuclear, that is, it consists of atoms of one chemical element, e.g. two atoms in the oxygen molecule (O2); or it may be heteronuclear, a chemical compound composed of more than one element, e.g. water (two hydrogen atoms and one oxygen atom; H2O). In the kinetic theory of gases, the term ''molecule'' is often used for any gaseous particle regardless of its composition. This relaxes the requirement that a molecule contains two or more atoms, since the noble gases are individual atoms. Atoms and complexes connected by non-covalent interactions, such as hydrogen bonds or ionic bonds, are typically not c ...
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Alzheimer's Disease
Alzheimer's disease (AD) is a 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 remembering recent events. As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and 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 allele of APOE. Other risk factors include a history of head injury, clinical depression, and high blood pre ...
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Amyloid Beta
Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ in a cholesterol-dependent process and substrate presentation. Aβ molecules can aggregate to form flexible soluble oligomers which may exist in several forms. It is now believed that certain misfolded oligomers (known as "seeds") can induce other Aβ molecules to also take the misfolded oligomeric form, leading to a chain reaction akin to a prion infection. The oligomers are toxic to nerve cells. The other protein implicated in Alzheimer's disease, tau protein, also forms such prion-like misfolded oligomers, and there is some evidence that misfolded Aβ can induce tau to misfold. A study has suggested that APP and its amyloid potential is of ancient origins, dating as far ba ...
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NLRP3
NLR family pyrin domain containing 3 (NLRP3) (previously known as NACHT, LRR and PYD domains-containing protein 3 ALP3and cryopyrin), is a protein that in humans is encoded by the ''NLRP3'' gene located on the long arm of chromosome 1. NLRP3 is expressed predominantly in macrophages and as a component of the inflammasome, detects products of damaged cells such as extracellular ATP and crystalline uric acid. Activated NLRP3 in turn triggers an immune response. Mutations in the NLRP3 gene are associated with a number of organ specific autoimmune diseases. Nomenclature NACHT, LRR, and PYD are respectively acronyms for: * NACHT – NAIP (neuronal apoptosis inhibitor protein), C2TA heterokaryon_incompatibility)_and_TP1_(telomerase-associated_protein_1) *_ MHC,_HET-E_(Podospora_anserina#Heterokaryon_incompatibility">heterokaryon_incompatibility)_and_TP1_(telomerase-associated_protein_1) *_Leucine-rich_repeat">LRR_–_"leucine-rich_repeat"__and_is_synonymous_with_NLR,_for_''_or_ ...
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Insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of glucose from the blood into liver, fat and skeletal muscle cells. In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both. Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especial ...
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