Alagebrium
Alagebrium (formerly known as ALT-711, dimethyl-3-N-phenacylthiazolium chloride) was a drug candidate developed by Alteon, Inc. It was the first drug candidate to be clinically tested for the purpose of breaking the crosslinks caused by advanced glycation endproducts (AGEs), thereby reversing one of the main mechanisms of aging. Through this effect Alagebrium is designed to reverse the stiffening of blood vessel walls that contributes to hypertension and cardiovascular disease, as well as many other forms of degradation associated with protein crosslinking. Alagebrium has proven effective in reducing systolic blood pressure and providing therapeutic benefit for patients with diastolic heart failure. Mechanism Advanced glycation end-products (AGEs) are proteins that become glycated as a result of exposure to sugars. They are a bio-marker implicated in aging and the development, or worsening, of many degenerative diseases, such as diabetes, atherosclerosis, chronic kidney di ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Advanced Glycation Endproduct
Advanced glycation end-products (AGEs) are proteins or lipids that become glycated as a result of exposure to sugars. They are a bio-marker implicated in aging and the development, or worsening, of many degenerative diseases, such as diabetes, atherosclerosis, chronic kidney disease, and Alzheimer's disease. Dietary sources Animal-derived foods that are high in fat and protein are generally AGE-rich and are prone to further AGE formation during cooking. However, only low molecular weight AGEs are absorbed through diet, and vegetarians have been found to have higher concentrations of overall AGEs compared to non-vegetarians. Therefore, it is unclear whether dietary AGEs contribute to disease and aging, or whether only endogenous AGEs (those produced in the body) matter. This does not free diet from potentially negatively influencing AGE, but potentially implies that dietary AGE may deserve less attention than other aspects of diet that lead to elevated blood sugar levels and format ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Glucosepane
Glucosepane is a lysine-arginine protein cross-linking product and advanced glycation end product (AGE) derived from D-glucose. It is an irreversible, covalent cross-link product that has been found to make intermolecular and intramolecular cross-links in the collagen of the extracellular matrix (ECM) and crystallin of the eyes. Covalent protein cross-links irreversibly link proteins together in the ECM of tissues. Glucosepane is present in human tissues at levels 10 to 1000 times higher than any other cross-linking AGE, and is currently considered to be the most important cross-linking AGE. Role in aging Aging leads to progressive loss of elasticity and stiffening of tissues rich in the ECM such as joints, cartilage, arteries, lungs and skin. It has been shown that these effects are brought about by the accumulation of cross-links in the ECM on long-lived proteins. Studies done on glucosepane by the Monnier group have shown that the level of glucosepane cross-links in human co ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Advanced Glycation End-product
Advanced glycation end-products (AGEs) are proteins or lipids that become Glycation, glycated as a result of exposure to sugars. They are a bio-marker implicated in aging and the development, or worsening, of many degenerative diseases, such as diabetes, atherosclerosis, chronic kidney disease, and Alzheimer's disease. Dietary sources Animal-derived foods that are high in fat and protein are generally AGE-rich and are prone to further AGE formation during cooking. However, only low molecular weight AGEs are absorbed through diet, and vegetarians have been found to have higher concentrations of overall AGEs compared to non-vegetarians. Therefore, it is unclear whether dietary AGEs contribute to disease and aging, or whether only endogenous AGEs (those produced in the body) matter. This does not free diet from potentially negatively influencing AGE, but potentially implies that dietary AGE may deserve less attention than other aspects of diet that lead to elevated Blood sugar level, b ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Glycation
Glycation (non-enzymatic glycosylation) is the covalent bond, covalent attachment of a sugar to a protein, lipid or nucleic acid molecule. Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is the non-enzymatic process responsible for many (e.g. micro and macrovascular) complications in diabetes mellitus and is implicated in some diseases and in aging. Glycation end products are believed to play a causative role in the vascular complications of diabetes mellitus. In contrast with glycation, glycosylation is the enzyme-mediated ATP-dependent attachment of sugars to a protein or lipid. Glycosylation occurs at defined sites on the target molecule. It is a common form of post-translational modification of proteins and is required for the functioning of the mature protein. Biochemistry Glycations occur mainly in the bloodstream to a small proportion of the absorbed simple sugars: glucose, fructose, and galactose. It appears that fru ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Chronic Kidney Disease
Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three months. Early in the course of CKD, patients are usually asymptomatic, but later symptoms may include pedal edema, leg swelling, feeling tired, vomiting, loss of appetite, and confusion. Complications can relate to hormonal dysfunction of the kidneys and include (in chronological order) Hypertension, high blood pressure (often related to activation of the renin–angiotensin system), renal osteodystrophy, bone disease, and anemia. Additionally CKD patients have markedly increased Cardiovascular disease, cardiovascular complications with increased risks of death and hospitalization. CKD can lead to kidney failure, end-stage kidney failure requiring kidney dialysis or kidney transplantation. Causes of chronic kidney disease include diabetic ne ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Glycosylation
Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not always in chemistry), glycosylation usually refers to an enzyme-catalysed reaction, whereas glycation (also 'non-enzymatic glycation' and 'non-enzymatic glycosylation') may refer to a non-enzymatic reaction. Glycosylation is a form of co-translational and post-translational modification. Glycans serve a variety of structural and functional roles in membrane and secreted proteins. The majority of proteins synthesized in the rough endoplasmic reticulum undergo glycosylation. Glycosylation is also present in the cytoplasm and nucleus as the ''O''-GlcNAc modification. Aglycosylation is a feature of engineered antibodies to bypass glycosylation. Five classes of glycans are produced: * ''N''-linked glycans attached to a nitrogen of asparagi ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Haptoglobin
Haptoglobin (abbreviated as Hp) is the protein that in humans is encoded by the ''HP'' gene. In blood plasma, haptoglobin binds with high affinity to ''free'' hemoglobin released from erythrocytes, and thereby inhibits its deleterious oxidative activity. Compared to Hp, hemopexin binds to ''free'' heme. The haptoglobin-hemoglobin complex will then be removed by the reticuloendothelial system (mostly the spleen). In clinical settings, the haptoglobin assay is used to screen for and monitor intravascular hemolytic anemia. In intravascular hemolysis, free hemoglobin will be released into circulation and hence haptoglobin will bind the hemoglobin. This causes a decline in haptoglobin levels. The protein was discovered as a "plasma substance" in 1938 by French biochemists Max-Fernand Jayle and Michel Polonovski. Function Hemoglobin that has been released into the blood plasma by damaged red blood cells has harmful effects. The ''HP'' gene encodes a preproprotein that is proc ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Alzheimer's Disease
Alzheimer's disease (AD) is a neurodegenerative disease and 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 average life expectancy following diagnosis is three to twelve years. The causes of Alzheimer's disease remain poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an allele of apolipoprotein E. Other risk factors include a history of head injury, clinical depression, and high blood pressure. The progression of the di ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Diabetes
Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of the body becoming unresponsive to insulin's effects. Classic symptoms include polydipsia (excessive thirst), polyuria (excessive urination), polyphagia (excessive hunger), weight loss, and blurred vision. If left untreated, the disease can lead to various health complications, including disorders of the cardiovascular system, eye, kidney, and nerves. Diabetes accounts for approximately 4.2 million deaths every year, with an estimated 1.5 million caused by either untreated or poorly treated diabetes. The major types of diabetes are type 1 and type 2. The most common treatment for type 1 is insulin replacement therapy (insulin injections), while anti-diabetic medications (such as metformin and semaglutide) and lifestyle modificatio ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by elevated blood levels of cholesterol. These lesions may lead to narrowing of the arterial walls due to buildup of atheromatous plaques. At the onset, there are usually no symptoms, but if they develop, symptoms generally begin around middle age. In severe cases, it can result in coronary artery disease, stroke, peripheral artery disease, or kidney disorders, depending on which body part(s) the affected arteries are located in the body. The exact cause of atherosclerosis is unknown and is proposed to be multifactorial. Risk factors include dyslipidemia, abnormal cholesterol levels, elevated levels of inflammatory biomarkers, high blood pressure, diabetes, smoking (both active and passive smoking), obesity, genetic factors, family history, lifes ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |