Advanced glycation end-product

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Advanced glycation end products (AGEs) are proteins or lipids that become glycated as a result of exposure to sugars. [1] 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. [2]

Contents

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. [3] 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. [4] Therefore, it is unclear whether dietary AGEs contribute to disease and aging, or whether only endogenous AGEs (those produced in the body) matter. [5] 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 formation of AGEs. [4] [5]

Effects

Glycation often entails the modification of the guanidine group of arginine residues with glyoxal (R = H), methylglyoxal (R = Me), and 3-deoxyglucosone, which arise from the metabolism of high-carbohydrate diets. Thus modified, these proteins contribute to complications from diabetes. Argpyrimidine Hydroimidazolone.png
Glycation often entails the modification of the guanidine group of arginine residues with glyoxal (R = H), methylglyoxal (R = Me), and 3-deoxyglucosone, which arise from the metabolism of high-carbohydrate diets. Thus modified, these proteins contribute to complications from diabetes.

AGEs affect nearly every type of cell and molecule in the body and are thought to be one factor in aging [6] and some age-related chronic diseases. [7] [8] [9] They are also believed to play a causative role in the vascular complications of diabetes mellitus. [10]

AGEs arise under certain pathologic conditions, such as oxidative stress due to hyperglycemia in patients with diabetes. [11] AGEs play a role as proinflammatory mediators in gestational diabetes as well. [12]

In the context of cardiovascular disease, AGEs can induce crosslinking of collagen, which can cause vascular stiffening and entrapment of low-density lipoprotein particles (LDL) in the artery walls. AGEs can also cause glycation of LDL which can promote its oxidation. [13] Oxidized LDL is one of the major factors in the development of atherosclerosis. [14] Finally, AGEs can bind to RAGE (receptor for advanced glycation end products) and cause oxidative stress as well as activation of inflammatory pathways in vascular endothelial cells. [13] [14]

In other diseases

AGEs have been implicated in Alzheimer's Disease, [15] cardiovascular disease, [16] and stroke. [17] The mechanism by which AGEs induce damage is through a process called cross-linking that causes intracellular damage and apoptosis. [18] They form photosensitizers in the crystalline lens, [19] which has implications for cataract development. [20] Reduced muscle function is also associated with AGEs. [21]

Pathology

AGEs have a range of pathological effects, such as: [22] [23]

Reactivity

Proteins are usually glycated through their lysine residues. [29] In humans, histones in the cell nucleus are richest in lysine, and therefore form the glycated protein N(6)-Carboxymethyllysine (CML). [29]

A receptor nicknamed RAGE, from receptor for advanced glycation end products, is found on many cells, including endothelial cells, smooth muscle, cells of the immune system [ which? ] from tissue such as lung, liver, and kidney.[ clarification needed ][ which? ] This receptor, when binding AGEs, contributes to age- and diabetes-related chronic inflammatory diseases such as atherosclerosis, asthma, arthritis, myocardial infarction, nephropathy, retinopathy, periodontitis and neuropathy. [30] The pathogenesis of this process hypothesized to activation of the nuclear factor kappa B (NF-κB) following AGE binding. [31] NF-κB controls several genes which are involved in inflammation. [32] AGEs can be detected and quantified using bioanalytical and immunological methods. [33]

Clearance

In clearance, or the rate at which a substance is removed or cleared from the body, it has been found that the cellular proteolysis of AGEs—the breakdown of proteins—produces AGE peptides and "AGE free adducts" (AGE adducts bound to single amino acids). These latter, after being released into the plasma, can be excreted in the urine. [34]

1. Renal pyramid * 2. Interlobular artery * 3. Renal artery * 4. Renal vein 5. Renal hilum * 6. Renal pelvis * 7. Ureter * 8. Minor calyx * 9. Renal capsule * 10. Inferior renal capsule * 11. Superior renal capsule * 12. Interlobular vein * 13. Nephron * 14. Minor calyx * 15. Major calyx * 16. Renal papilla * 17. Renal column KidneyStructures PioM.svg
1.  Renal pyramid • 2.  Interlobular artery • 3.  Renal artery • 4.  Renal vein 5.  Renal hilum • 6.  Renal pelvis • 7.  Ureter • 8.  Minor calyx • 9.  Renal capsule • 10.  Inferior renal capsule • 11.  Superior renal capsule • 12.  Interlobular vein • 13.  Nephron • 14.  Minor calyx • 15.  Major calyx • 16.  Renal papilla • 17.  Renal column

Nevertheless, the resistance of extracellular matrix proteins to proteolysis renders their advanced glycation end products less conducive to being eliminated. [34] While the AGE free adducts are released directly into the urine, AGE peptides are endocytosed by the epithelial cells of the proximal tubule and then degraded by the endolysosomal system to produce AGE amino acids. It is thought that these acids are then returned to the kidney's inside space, or lumen, for excretion. [22] AGE free adducts are the major form through which AGEs are excreted in urine, with AGE-peptides occurring to a lesser extent [22] but accumulating in the plasma of patients with chronic kidney failure. [34]

Larger, extracellularly derived AGE proteins cannot pass through the basement membrane of the renal corpuscle and must first be degraded into AGE peptides and AGE free adducts. Peripheral macrophage [22] as well as liver sinusoidal endothelial cells and Kupffer cells [35] have been implicated in this process, although the real-life involvement of the liver has been disputed. [36]

Endothelial cell Endotelijalna celija.jpg
Endothelial cell

Large AGE proteins unable to enter the Bowman's capsule are capable of binding to receptors on endothelial and mesangial cells and to the mesangial matrix. [22] Activation of RAGE induces production of a variety of cytokines, including TNFβ, which mediates an inhibition of metalloproteinase and increases production of mesangial matrix, leading to glomerulosclerosis [23] and decreasing kidney function in patients with unusually high AGE levels.

Although the only form suitable for urinary excretion, the breakdown products of AGE—that is, peptides and free adducts—are more aggressive than the AGE proteins from which they are derived, and they can perpetuate related pathology in diabetic patients, even after hyperglycemia has been brought under control. [22]

Some AGEs have an innate catalytic oxidative capacity, while activation of NAD(P)H oxidase through activation of RAGE and damage to mitochondrial proteins leading to mitochondrial dysfunction can also induce oxidative stress. A 2007 in vitro study found that AGEs could significantly increase expression of TGF-β1, CTGF, Fn mRNA in NRK-49F cells through enhancement of oxidative stress, and suggested that inhibition of oxidative stress might underlie the effect of ginkgo biloba extract in diabetic nephropathy. The authors suggested that antioxidant therapy might help prevent the accumulation of AGEs and induced damage. [23] In the end, effective clearance is necessary, and those suffering AGE increases because of kidney dysfunction might require a kidney transplant. [22]

In diabetics who have an increased production of an AGE, kidney damage reduces the subsequent urinary removal of AGEs, forming a positive feedback loop that increases the rate of damage. In a 1997 study, diabetic and healthy subjects were given a single meal of egg white (56 g protein), cooked with or without 100 g of fructose; there was a greater than 200-fold increase in AGE immunoreactivity from the meal with fructose. [37]

Potential therapy

Diagram of a resveratrol molecule Resveratrol.svg
Diagram of a resveratrol molecule

AGEs are the subject of ongoing research. There are three therapeutic approaches: preventing the formation of AGEs, breaking crosslinks after they are formed and preventing their negative effects.

Compounds that have been found to inhibit AGE formation in the laboratory include Vitamin C, Agmatine, benfotiamine, pyridoxamine, alpha-lipoic acid, [38] [39] taurine, [40] pimagedine, [41] aspirin, [42] [43] carnosine, [44] metformin, [45] pioglitazone, [45] and pentoxifylline. [45] Activation of the TRPA-1 receptor by lipoic acid or podocarpic acid has been shown to reduce the levels of AGES by enhancing the detoxification of methylglyoxal, a major precursor of several AGEs. [38]

Studies in rats and mice have found that natural phenols such as resveratrol and curcumin can prevent the negative effects of the AGEs. [46] [47]

Compounds that are thought to break some existing AGE crosslinks include Alagebrium (and related ALT-462, ALT-486, and ALT-946) [48] and N-phenacyl thiazolium bromide. [49] One in vitro study shows that rosmarinic acid out performs the AGE breaking potential of ALT-711. [50]

Diagram of a glucosepane molecule Glucosepane.svg
Diagram of a glucosepane molecule

There is, however, no agent known that can break down the most common AGE, glucosepane, which appears 10 to 1,000 times more common in human tissue than any other cross-linking AGE. [51] [52]

Some chemicals, on the other hand, like aminoguanidine, might limit the formation of AGEs by reacting with 3-deoxyglucosone. [30]

See also

Related Research Articles

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<span class="mw-page-title-main">3-Deoxyglucosone</span> Chemical compound

3-Deoxyglucosone (3DG) is a sugar that is notable because it is a marker for diabetes. 3DG reacts with protein to form advanced glycation end-products (AGEs), which contribute to diseases such as the vascular complications of diabetes, atherosclerosis, hypertension, Alzheimer's disease, inflammation, and aging.

<span class="mw-page-title-main">Argpyrimidine</span> Chemical compound

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<span class="mw-page-title-main">Reactive carbonyl species</span>

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Azeliragon is a small-molecule RAGE inhibitor. It is developed by vTv Therapeutics for various cancers, including triple-negative breast cancer, pancreatic cancer.

References

  1. ↑ Goldin, Alison; Beckman, Joshua A.; Schmidt, Ann Marie; Creager, Mark A. (2006). "Advanced Glycation End Products Sparking the Development of Diabetic Vascular Injury". Circulation. 114 (6): 597–605. doi: 10.1161/CIRCULATIONAHA.106.621854 . PMID   16894049.
  2. ↑ Vistoli, G; De Maddis, D; Cipak, A; Zarkovic, N; Carini, M; Aldini, G (Aug 2013). "Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): an overview of their mechanisms of formation" (PDF). Free Radic Res. 47: Suppl 1:3–27. doi:10.3109/10715762.2013.815348. PMID   23767955. S2CID   207517855.
  3. ↑ Uribarri, Jaime; Woodruff, Sandra; Goodman, Susan; Cai, Weijing; Chen, Xue; Pyzik, Renata; Yong, Angie; Striker, Gary E.; Vlassara, Helen (June 2010). "Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet". Journal of the American Dietetic Association. 110 (6): 911–916.e12. doi:10.1016/j.jada.2010.03.018. PMC   3704564 . PMID   20497781.
  4. 1 2 Poulsen, Malene W.; Hedegaard, Rikke V.; Andersen, Jeanette M.; de Courten, Barbora; Bügel, Susanne; Nielsen, John; Skibsted, Leif H.; Dragsted, Lars O. (October 2013). "Advanced glycation endproducts in food and their effects on health". Food and Chemical Toxicology. 60: 10–37. doi:10.1016/j.fct.2013.06.052. PMID   23867544.
  5. 1 2 Luevano-Contreras, Claudia; Chapman-Novakofski, Karen (13 December 2010). "Dietary Advanced Glycation End Products and Aging". Nutrients. 2 (12): 1247–1265. doi: 10.3390/nu2121247 . PMC   3257625 . PMID   22254007.
  6. ↑ Chaudhuri, Jyotiska; Bains, Yasmin; Guha, Sanjib; Kahn, Arnold; Hall, David; Bose, Neelanjan; Gugliucci, Alejandro; Kapahi, Pankaj (4 September 2018). "The role of advanced glycation end products in aging and metabolic diseases: bridging association and causality". Cell Metabolism. 28 (3): 337–352. doi:10.1016/j.cmet.2018.08.014. PMC   6355252 . PMID   30184484.
  7. ↑ Glenn, J.; Stitt, A. (2009). "The role of advanced glycation end products in retinal ageing and disease". Biochimica et Biophysica Acta (BBA) - General Subjects. 1790 (10): 1109–1116. doi:10.1016/j.bbagen.2009.04.016. PMID   19409449.
  8. ↑ Semba, R. D.; Ferrucci, L.; Sun, K.; Beck, J.; Dalal, M.; Varadhan, R.; Walston, J.; Guralnik, J. M.; Fried, L. P. (2009). "Advanced glycation end products and their circulating receptors predict cardiovascular disease mortality in older community-dwelling women". Aging Clinical and Experimental Research. 21 (2): 182–190. doi:10.1007/BF03325227. PMC   2684987 . PMID   19448391.
  9. ↑ Semba, R.; Najjar, S.; Sun, K.; Lakatta, E.; Ferrucci, L. (2009). "Serum carboxymethyl-lysine, an advanced glycation end product, is associated with increased aortic pulse wave velocity in adults". American Journal of Hypertension. 22 (1): 74–79. doi:10.1038/ajh.2008.320. PMC   2637811 . PMID   19023277.
  10. ↑ Yan, S. F.; D'Agati, V.; Schmidt, A. M.; Ramasamy, R. (2007). "Receptor for Advanced Glycation Endproducts (RAGE): a formidable force in the pathogenesis of the cardiovascular complications of diabetes & aging". Current Molecular Medicine. 7 (8): 699–710. doi:10.2174/156652407783220732. PMID   18331228.
  11. ↑ Brownlee, M (June 2005). "The pathobiology of diabetic complications: a unifying mechanism". Diabetes. 54 (6): 1615–25. doi: 10.2337/diabetes.54.6.1615 . PMID   15919781.
  12. ↑ Pertyńska-Marczewska, Magdalena; Głowacka, Ewa; Sobczak, Małgorzata; Cypryk, Katarzyna; Wilczyński, Jan (11 January 2009). "Glycation Endproducts, Soluble Receptor for Advanced Glycation Endproducts and Cytokines in Diabetic and Non-diabetic Pregnancies". American Journal of Reproductive Immunology. 61 (2): 175–182. doi:10.1111/j.1600-0897.2008.00679.x. PMID   19143681. S2CID   3186554.
  13. 1 2 Prasad, Anand; Bekker, Peter; Tsimikas, Sotirios (2012). "Advanced Glycation End Products and Diabetic Cardiovascular Disease". Cardiology in Review. 20 (4): 177–183. doi:10.1097/CRD.0b013e318244e57c. PMID   22314141. S2CID   8471652.
  14. 1 2 Di Marco, Elyse; Gray, Stephen P.; Jandeleit-Dahm, Karin (2013). "Diabetes Alters Activation and Repression of Pro- and Anti-Inflammatory Signaling Pathways in the Vasculature". Frontiers in Endocrinology. 4: 68. doi: 10.3389/fendo.2013.00068 . PMC   3672854 . PMID   23761786.
  15. ↑ Srikanth, Velandai; Maczurek, Annette; Phan, Thanh; Steele, Megan; Westcott, Bernadette; Juskiw, Damian; Münch, Gerald (May 2011). "Advanced glycation endproducts and their receptor RAGE in Alzheimer's disease". Neurobiology of Aging. 32 (5): 763–777. doi:10.1016/j.neurobiolaging.2009.04.016. PMID   19464758. S2CID   207158367.
  16. ↑ Simm, A.; Wagner, J.; Gursinsky, T.; Nass, N.; Friedrich, I.; Schinzel, R.; Czeslik, E.; Silber, R.E.; Scheubel, R.J. (July 2007). "Advanced glycation endproducts: A biomarker for age as an outcome predictor after cardiac surgery?". Experimental Gerontology. 42 (7): 668–675. doi:10.1016/j.exger.2007.03.006. PMID   17482402. S2CID   30264495.
  17. ↑ Zimmerman, G A; Meistrell, M; Bloom, O; Cockroft, K M; Bianchi, M; Risucci, D; Broome, J; Farmer, P; Cerami, A; Vlassara, H (25 April 1995). "Neurotoxicity of advanced glycation endproducts during focal stroke and neuroprotective effects of aminoguanidine". Proceedings of the National Academy of Sciences of the United States of America. 92 (9): 3744–3748. Bibcode:1995PNAS...92.3744Z. doi: 10.1073/pnas.92.9.3744 . PMC   42038 . PMID   7731977.
  18. ↑ Shaikh, Shamim; Nicholson, Louise F.B. (July 2008). "Advanced glycation end products induce in vitro cross‐linking of α‐synuclein and accelerate the process of intracellular inclusion body formation". Journal of Neuroscience Research. 86 (9): 2071–2082. doi:10.1002/jnr.21644. PMID   18335520. S2CID   37510479.
  19. ↑ Fuentealba, Denis; Friguet, Bertrand; Silva, Eduardo (January 2009). "Advanced Glycation Endproducts Induce Photocrosslinking and Oxidation of Bovine Lens Proteins Through Type-I Mechanism". Photochemistry and Photobiology. 85 (1): 185–194. doi: 10.1111/j.1751-1097.2008.00415.x . PMID   18673320.
  20. ↑ Gul, Anjuman; Rahman, M. Ataur; Hasnain, Syed Nazrul (6 February 2009). "Role of fructose concentration on cataractogenesis in senile diabetic and non-diabetic patients". Graefe's Archive for Clinical and Experimental Ophthalmology. 247 (6): 809–814. doi:10.1007/s00417-008-1027-9. PMID   19198870. S2CID   9260375.
  21. ↑ Haus, Jacob M.; Carrithers, John A.; Trappe, Scott W.; Trappe, Todd A. (December 2007). "Collagen, cross-linking, and advanced glycation end products in aging human skeletal muscle". Journal of Applied Physiology. 103 (6): 2068–2076. doi:10.1152/japplphysiol.00670.2007. PMID   17901242.
  22. 1 2 3 4 5 6 7 Gugliucci A, Bendayan M (1996). "Renal fate of circulating advanced glycated end products (AGE): evidence for reabsorption and catabolism of AGE peptides by renal proximal tubular cells". Diabetologia. 39 (2): 149–60. doi: 10.1007/BF00403957 . PMID   8635666.
  23. 1 2 3 Yan, Hai-dong; Li, Xue-zhu; Xie, Jun-mei; Li, Man (May 2007). "Effects of advanced glycation end products on renal fibrosis and oxidative stress in cultured NRK-49F cells". Chinese Medical Journal. 120 (9): 787–793. doi: 10.1097/00029330-200705010-00010 . PMID   17531120.
  24. ↑ Kostolanská J, Jakus V, Barák L (May 2009). "HbA1c and serum levels of advanced glycation and oxidation protein products in poorly and well controlled children and adolescents with type 1 diabetes mellitus". Journal of Pediatric Endocrinology & Metabolism. 22 (5): 433–42. doi:10.1515/JPEM.2009.22.5.433. PMID   19618662. S2CID   23150519.
  25. ↑ Ninomiya, T.; et al. (2001). "A novel AGE production inhibitor, prevents progression of diabetic nephropathy in STZ-induced rats". Diabetes. 50 Suppl. (2): A178–179.
  26. 1 2 Bierhaus A, Hofmann MA, Ziegler R, Nawroth PP (March 1998). "AGEs and their interaction with AGE-receptors in vascular disease and diabetes mellitus. I. The AGE concept". Cardiovascular Research. 37 (3): 586–600. doi: 10.1016/S0008-6363(97)00233-2 . PMID   9659442.
  27. ↑ Thornalley, P.J. (1996). "Advanced glycation and the development of diabetic complications. Unifying the involvement of glucose, methylglyoxal and oxidative stress". Endocrinol. Metab. 3: 149–166.
  28. ↑ Hofmann MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, Avila C, Kambham N, Bierhaus A, Nawroth P, Neurath MF, Slattery T, Beach D, McClary J, Nagashima M, Morser J, Stern D, Schmidt AM (June 1999). "RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides". Cell. 97 (7): 889–901. doi: 10.1016/S0092-8674(00)80801-6 . PMID   10399917. S2CID   7208198.
  29. 1 2 Ansari NA, Moinuddin, Ali R (2011). "Glycated lysine residues: a marker for non-enzymatic protein glycation in age-related diseases". Disease Markers. 30 (6): 317–324. doi: 10.1155/2011/718694 . PMC   3825483 . PMID   21725160.
  30. 1 2 Wells-Knecht KJ, Zyzak DV, Litchfield JE, Thorpe SR, Baynes JW (1995). "Mechanism of autoxidative glycosylation: identification of glyoxal and arabinose as intermediates in the autoxidative modification of proteins by glucose". Biochemistry . 34 (11): 3702–9. doi:10.1021/bi00011a027. PMID   7893666.
  31. ↑ Huttunen, Henri J.; Fages, Carole; Rauvala, Heikki (July 1999). "Receptor for Advanced Glycation End Products (RAGE)-mediated Neurite Outgrowth and Activation of NF-κB Require the Cytoplasmic Domain of the Receptor but Different Downstream Signaling Pathways". Journal of Biological Chemistry. 274 (28): 19919–19924. doi: 10.1074/jbc.274.28.19919 .
  32. ↑ Liu, Ting; Zhang, Lingyun; Joo, Donghyun; Sun, Shao-Cong (December 2017). "NF-κB signaling in inflammation". Signal Transduction and Targeted Therapy. 2 (1): 17023. doi: 10.1038/sigtrans.2017.23 .
  33. ↑ Ashraf, Jalaluddin Mohd.; Ahmad, Saheem; Choi, Inho; Ahmad, Nashrah; Farhan, Mohd.; Tatyana, Godovikova; Shahab, Uzma (November 2015). "Recent advances in detection of AGEs: Immunochemical, bioanalytical and biochemical approaches: Technological Progress in Age Detection". IUBMB Life. 67 (12): 897–913. doi: 10.1002/iub.1450 .
  34. 1 2 3 Gugliucci A, Mehlhaff K, Kinugasa E, et al. (2007). "Paraoxonase-1 concentrations in end-stage renal disease patients increase after hemodialysis: correlation with low molecular AGE adduct clearance". Clin. Chim. Acta. 377 (1–2): 213–20. doi:10.1016/j.cca.2006.09.028. PMID   17118352.
  35. ↑ Smedsrød B, Melkko J, Araki N, Sano H, Horiuchi S (1997). "Advanced glycation end products are eliminated by scavenger-receptor-mediated endocytosis in hepatic sinusoidal Kupffer and endothelial cells". Biochem. J. 322 (Pt 2): 567–73. doi:10.1042/bj3220567. PMC   1218227 . PMID   9065778.
  36. ↑ Svistounov D, Smedsrød B (2004). "Hepatic clearance of advanced glycation end products (AGEs)—myth or truth?". J. Hepatol. 41 (6): 1038–40. doi: 10.1016/j.jhep.2004.10.004 . PMID   15582139.
  37. ↑ Koschinsky, Theodore; He, Ci-Jiang; Mitsuhashi, Tomoko; Bucala, Richard; Liu, Cecilia; Buenting, Christina; Heitmann, Kirsten; Vlassara, Helen (10 June 1997). "Orally absorbed reactive glycation products (glycotoxins): An environmental risk factor in diabetic nephropathy". Proceedings of the National Academy of Sciences of the United States of America. 94 (12): 6474–6479. Bibcode:1997PNAS...94.6474K. doi: 10.1073/pnas.94.12.6474 . PMC   21074 . PMID   9177242.
  38. 1 2 Chaudhuri, Jyotiska; Bose, Neelanjan; Gong, Jianke; Hall, David; Rifkind, Alexander; Bhaumik, Dipa; Peiris, T. Harshani; Chamoli, Manish; Le, Catherine H.; Liu, Jianfeng; Lithgow, Gordon J.; Ramanathan, Arvind; Shawn Xu, X. Z.; Kapahi, Pankaj (21 November 2016). "A Caenorhabditis elegans Model Elucidates a Conserved Role for TRPA1-Nrf Signaling in Reactive Alpha-dicarbonyl Detoxification". Current Biology. 26 (22): 3014–3025. doi:10.1016/j.cub.2016.09.024. PMC   5135008 . PMID   27773573.
  39. ↑ Mohmmad Abdul, Hafiz; Butterfield, D. Allan (February 2007). "Involvement of PI3K/PKG/ERK1/2 signaling pathways in cortical neurons to trigger protection by cotreatment of acetyl-L-carnitine and α-lipoic acid against HNE-mediated oxidative stress and neurotoxicity: Implications for Alzheimer's disease". Free Radical Biology and Medicine. 42 (3): 371–384. doi:10.1016/j.freeradbiomed.2006.11.006. PMC   1808543 . PMID   17210450.
  40. ↑ Nandhini AT, Thirunavukkarasu V, Anuradha CV (August 2005). "Taurine prevents collagen abnormalities in high fructose-fed rats" (PDF). Indian J. Med. Res. 122 (2): 171–7. PMID   16177476. Archived from the original (PDF) on 2009-04-17. Retrieved 2009-04-16.
  41. ↑ A. Gugliucci, "Sour Side of Sugar, A Glycation Web Page Archived July 1, 2007, at the Wayback Machine
  42. ↑ Urios, P.; Grigorova-Borsos, A.-M.; Sternberg, M. (2007). "Aspirin inhibits the formation of... preview & related info". Diabetes Research and Clinical Practice. 77 (2): 337–340. doi:10.1016/j.diabres.2006.12.024. PMID   17383766 . Retrieved 2013-11-13.
  43. ↑ Bucala, Richard; Cerami, Anthony (1992). Advanced Glycosylation: Chemistry, Biology, and Implications for Diabetes and Aging. Advances in Pharmacology. Vol. 23. pp. 1–34. doi:10.1016/S1054-3589(08)60961-8. ISBN   978-0-12-032923-6. PMID   1540533.
  44. ↑ Guiotto, Andrea; Calderan, Andrea; Ruzza, Paolo; Borin, Gianfranco (1 September 2005). "Carnosine and Carnosine-Related Antioxidants: A Review". Current Medicinal Chemistry. 12 (20): 2293–2315. doi:10.2174/0929867054864796. PMID   16181134.
  45. 1 2 3 Rahbar, S; Figarola, JL (2013-03-25). "Novel inhibitors of advanced glycation endproducts". Arch. Biochem. Biophys. 419 (1): 63–79. doi:10.1016/j.abb.2003.08.009. PMID   14568010.
  46. ↑ Mizutani, Kenichi; Ikeda, Katsumi; Yamori, Yukio (July 2000). "Resveratrol Inhibits AGEs-Induced Proliferation and Collagen Synthesis Activity in Vascular Smooth Muscle Cells from Stroke-Prone Spontaneously Hypertensive Rats". Biochemical and Biophysical Research Communications. 274 (1): 61–67. doi:10.1006/bbrc.2000.3097. PMID   10903896.
  47. ↑ Tang, Youcai; Chen, Anping (10 March 2014). "Curcumin eliminates the effect of advanced glycation end-products (AGEs) on the divergent regulation of gene expression of receptors of AGEs by interrupting leptin signaling". Laboratory Investigation. 94 (5): 503–516. doi:10.1038/labinvest.2014.42. PMC   4006284 . PMID   24614199.
  48. ↑ Bakris, George L.; Bank, Alan J.; Kass, David A.; Neutel, Joel M.; Preston, Richard A.; Oparil, Suzanne (1 December 2004). "Advanced glycation end-product cross-link breakersA novel approach to cardiovascular pathologies related to the aging process". American Journal of Hypertension. 17 (S3): 23S–30S. doi: 10.1016/j.amjhyper.2004.08.022 . PMID   15607432.
  49. ↑ Vasan, Sara; Zhang, Xin; Zhang, Xini; Kapurniotu, Aphrodite; Bernhagen, Jürgen; Teichberg, Saul; Basgen, John; Wagle, Dilip; Shih, David; Terlecky, Ihor; Bucala, Richard; Cerami, Anthony; Egan, John; Ulrich, Peter (July 1996). "An agent cleaving glucose-derived protein crosslinks in vitro and in vivo". Nature. 382 (6588): 275–278. Bibcode:1996Natur.382..275V. doi:10.1038/382275a0. PMID   8717046. S2CID   4366953.
  50. ↑ Jean, Daniel; Pouligon, Maryse; Dalle, Claude (2015). "Evaluation in vitro of AGE-crosslinks breaking ability of rosmarinic acid". Glycative Stress Research. 2 (4): 204–207. doi:10.24659/gsr.2.4_204.
  51. ↑ Monnier, Vincent M.; Mustata, Georgian T.; Biemel, Klaus L.; Reihl, Oliver; Lederer, Marcus O.; Zhenyu, Dai; Sell, David R. (June 2005). "Cross-Linking of the Extracellular Matrix by the Maillard Reaction in Aging and Diabetes: An Update on 'a Puzzle Nearing Resolution'". Annals of the New York Academy of Sciences. 1043 (1): 533–544. Bibcode:2005NYASA1043..533M. doi:10.1196/annals.1333.061. PMID   16037276. S2CID   27507321.
  52. ↑ Furber, John D. (June 2006). "Extracellular Glycation Crosslinks: Prospects for Removal". Rejuvenation Research. 9 (2): 274–278. doi:10.1089/rej.2006.9.274. PMID   16706655.
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