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Advanced glycation end-products (AGEs): involvement in aging and in neurodegenerative diseases

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Summary.

Advanced glycation end-products (AGEs) are formed from the so-called Amadori products by rearrangement followed by other reactions giving rise to compounds bound irreversibly. The structure of some of them is shown and the mechanism of formation is described. Several AGE binding molecules (Receptors for AGE, RAGE) are known and it is thought that many of the effects caused by AGEs are mediated by RAGE. Some of these were shown to be toxic, and called TAGE. The mechanism of detoxification of glyoxal and methylglyoxal by the glyoxalase system is described and also the possibility to eliminate glycated proteins by deglycation enzymes. Compounds able to inhibit AGEs formation are also taken into consideration.

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References

  • N Ahmed PJ Thornalley R Luthen D Haussinger K Sebekova R Schinzel W Voelker A Heidland (2004) ArticleTitleProcessing of protein glycation, oxidation and nitrosation adducts in the liver and the effect of cirrhosis J Hepatol 41 913–919 Occurrence Handle15582123 Occurrence Handle10.1016/j.jhep.2004.08.007 Occurrence Handle1:CAS:528:DC%2BD2cXhtVCgsLzO

    Article  PubMed  CAS  Google Scholar 

  • TR Brown B Su KA Brown MA Scgwartz AM Tobia F Kappler (2003) ArticleTitleModulation of in vivo 3-deoxyglucosone levels Biochem Soc Trans 31 1433–1437 Occurrence Handle14641082 Occurrence Handle10.1042/BST0310543 Occurrence Handle1:CAS:528:DC%2BD3sXps12jtLg%3D

    Article  PubMed  CAS  Google Scholar 

  • F Chen MA Wollmer F Hoerndli G Münch B Kuhla ET Rogaev M Tsolaki A Papassotiropoulos J Götz (2004) ArticleTitleRole for glyoxalase I in Alzheimer’s disease Proc Natl Acad Sci USA 101 7687–7692 Occurrence Handle15128939 Occurrence Handle10.1073/pnas.0402338101 Occurrence Handle1:CAS:528:DC%2BD2cXktlOlurw%3D

    Article  PubMed  CAS  Google Scholar 

  • H Choei N Sasaki M Takeuchi T Yoshida W Ukai S Yamagishi S Kikuchi T Saito (2004) ArticleTitleGlyceraldehyde-derived advanced glycation end products in Alzheimer’s disease Acta Neuropathol 108 189–193 Occurrence Handle15221334 Occurrence Handle10.1007/s00401-004-0871-x Occurrence Handle1:CAS:528:DC%2BD2cXmt1Krtbc%3D

    Article  PubMed  CAS  Google Scholar 

  • F Collard E Wiame N Bergans J Fortpied D Vertommen F Vanstapel G Delpierre E Van Schaftingen (2004) ArticleTitleFructosamine 3-kinase-related protein and deglycation in human erythrocytes Biochem J 382 137143

    Google Scholar 

  • DJ Creighton Z-B Zheng R Holewinski DS Hamilton JL Eiseman (2003) ArticleTitleGlyoxalase I inhibitors in cancer chemotherapy Biochem Soc Trans 31 1378–1382 Occurrence Handle14641067 Occurrence Handle1:CAS:528:DC%2BD3sXps12jt74%3D Occurrence Handle10.1042/BST0311378

    Article  PubMed  CAS  Google Scholar 

  • Q Ding JN Keller (2005) ArticleTitleSplice variants of the receptor for advanced glycosylation end products (RAGE) in human brain Neurosci Lett 373 67–72 Occurrence Handle15555779 Occurrence Handle10.1016/j.neulet.2004.09.059 Occurrence Handle1:CAS:528:DC%2BD2cXhtVSktrbI

    Article  PubMed  CAS  Google Scholar 

  • S Dukic-Stefanovic R Schinzel P Riederer G Münch (2001) ArticleTitleAGES in brain ageing: AGE-inhibitors as neuroprotective and anti-dementia drugs? Biogerontology 2 19–34 Occurrence Handle11708614 Occurrence Handle10.1023/A:1010052800347 Occurrence Handle1:CAS:528:DC%2BD3MXitlequr0%3D

    Article  PubMed  CAS  Google Scholar 

  • A Gugliucci T Menini (2003) ArticleTitleThe polyamines spermine and spermidine protect proteins from structural and functional damage by AGE precursors: a new role for old molecules Life Sci 72 2603–2616 Occurrence Handle12672506 Occurrence Handle10.1016/S0024-3205(03)00166-8 Occurrence Handle1:CAS:528:DC%2BD3sXisV2ksrc%3D

    Article  PubMed  CAS  Google Scholar 

  • RG Khalifah JW Baynes BG Hudson (1999) ArticleTitleAmadorins: novel post-Amadori inhibitors of advanced glycation reactions Biochem Biophys Res Commun 257 251–258 Occurrence Handle10198198 Occurrence Handle10.1006/bbrc.1999.0371 Occurrence Handle1:CAS:528:DyaK1MXit1yksr8%3D

    Article  PubMed  CAS  Google Scholar 

  • B Khula H-J Lüth D Haferburg K Boeck T Arendt G Münch (2005) ArticleTitleMethylglyoxal, glyoxal, and their detoxification in Alzheimer’s disease Ann NY Acad Sci 1043 211–216 Occurrence Handle10.1196/annals.1333.026 Occurrence Handle1:CAS:528:DC%2BD2MXpvVKqsb8%3D

    Article  CAS  Google Scholar 

  • LW Ko EC Ko P Nacharaju WK Liu E Chang A Kenessey SH Yen (1999) ArticleTitleAn immunochemical study on tau glycation in paired helical filaments Brain Res 830 301–313 Occurrence Handle10366687 Occurrence Handle10.1016/S0006-8993(99)01415-8 Occurrence Handle1:CAS:528:DyaK1MXjtl2qsbs%3D

    Article  PubMed  CAS  Google Scholar 

  • B Kuhla K Boeck A Schmidt V Ogunlade T Arendt G Münch H-J Lüth (2007) ArticleTitleAge- and stage-dependent glyoxalase I expression and its activity in normal and Alzheimer’s disease brains Neurobiol Aging 28 29–41 Occurrence Handle16427160 Occurrence Handle10.1016/j.neurobiolaging.2005.11.007 Occurrence Handle1:CAS:528:DC%2BD28Xht1elt7bF

    Article  PubMed  CAS  Google Scholar 

  • H-J Lüth G Münch T Arendt (2002) ArticleTitleAberrant expression of NOS isoforms in Alzheimer’s disease is structurally related to nitrotyrosine formation Brain Res 953 135–143 Occurrence Handle12384247 Occurrence Handle10.1016/S0006-8993(02)03280-8

    Article  PubMed  Google Scholar 

  • GPK Marasinghe IM Sander B Bennett G Periyannan K-W Yang CA Makaroff MW Crowder (2005) ArticleTitleStructural studies on a mitochondrial glyoxalase II J Biol Chem 280 40668–40675 Occurrence Handle16227621 Occurrence Handle10.1074/jbc.M509748200 Occurrence Handle1:CAS:528:DC%2BD2MXht1OqtrfI

    Article  PubMed  CAS  Google Scholar 

  • JD Méndez LI Leal (2004) ArticleTitleInhibition of in vitro pyrraline formation by L-arginine and polyamines Biomed Pharmacother 58 598–604 Occurrence Handle15589069 Occurrence Handle10.1016/j.biopha.2004.09.004 Occurrence Handle1:CAS:528:DC%2BD2cXhtVGgurfO

    Article  PubMed  CAS  Google Scholar 

  • MJ Picklo SuffixSr SJ Olson WR Markesbery TJ Montine (2001) ArticleTitleExpression and activities of aldo-keto oxidoreductases in Alzheimer disease J Neuropathol Exp Neurol 60 686–694 Occurrence Handle11444797 Occurrence Handle1:CAS:528:DC%2BD3MXlt1yrsLs%3D

    PubMed  CAS  Google Scholar 

  • MJ Picklo SuffixSr TY Montine V Amarnath MD Neely (2002) ArticleTitleCarbonyl toxicology and Alzheimer’s disease Toxicol Appl Pharmacol 184 187–197 Occurrence Handle12460747 Occurrence Handle10.1006/taap.2002.9506 Occurrence Handle1:CAS:528:DC%2BD38XovVyiu7w%3D

    Article  PubMed  CAS  Google Scholar 

  • JP Richard (1993) ArticleTitleMechanism for the formation of methylglyoxal from triosephosphates Biochem Soc Trans 21 549–553 Occurrence Handle8359530 Occurrence Handle1:CAS:528:DyaK3sXkt1ehtrc%3D

    PubMed  CAS  Google Scholar 

  • P Riederer S Hoyer (2006) ArticleTitleFrom benefit to damage. Glutamate and advanced glycation end products in Alzheimer brain J Neural Transm 113 1671–1677 Occurrence Handle17053873 Occurrence Handle10.1007/s00702-006-0591-6 Occurrence Handle1:CAS:528:DC%2BD28XhtFegt7nE

    Article  PubMed  CAS  Google Scholar 

  • H Sakamoto T Mashima S Sato Y Hashimoto T Yamori T Tsuruo (2001) ArticleTitleSelective activation of apoptosis program by S-p-bromobenzylglutathione cyclopentyl diester in glyoxalase I – overexpressing human lung cancer cells Clin Cancer Res 7 2513–2518 Occurrence Handle11489834 Occurrence Handle1:CAS:528:DC%2BD3MXmsVOmtbg%3D

    PubMed  CAS  Google Scholar 

  • N Sasaki M Takeuchi H Chowei S Kikuchi Y Hayashi N Nakano H Ikeda S Yamagishi T Kitamoto T Saito Z Makita (2002) ArticleTitleAdvanced glycation end products (AGE) and their receptor (RAGE) in the brain of patients with Creutzfeldt-Jacob disease with prion plaques Neurosci Lett 326 117–120 Occurrence Handle12057842 Occurrence Handle10.1016/S0304-3940(02)00310-5 Occurrence Handle1:CAS:528:DC%2BD38XktFKgt7k%3D

    Article  PubMed  CAS  Google Scholar 

  • N Sasaki S Toki H Chowei T Saito N Nakano Y Hayashi M Takeuchi Z Makita (2001) ArticleTitleImmunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer’s disease Brain Res 888 256–262 Occurrence Handle11150482 Occurrence Handle10.1016/S0006-8993(00)03075-4 Occurrence Handle1:CAS:528:DC%2BD3MXitl2jsQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • T Sato M Iwaki N Shimogaito X Wu S Yamagishi M Takeuchi (2006) ArticleTitleTAGE (Toxic AGEs) theory in diabetic complications Curr Mol Med 6 351–358 Occurrence Handle16712480 Occurrence Handle10.2174/156652406776894536 Occurrence Handle1:CAS:528:DC%2BD28XlsVGmtr4%3D

    Article  PubMed  CAS  Google Scholar 

  • T Sato N Shimogaito X Wu S Kikuchi S Yamagishi M Takeuchi (2006) ArticleTitleToxic advanced glycation end products (TAGE) theory in Alzheimer’s disease Am J Alzheimers Dis Other Demen 21 197–208 Occurrence Handle16869341 Occurrence Handle10.1177/1533317506289277

    Article  PubMed  Google Scholar 

  • AM Schmidt DM Stern (2000) ArticleTitleRAGE: a new target for the prevention and treatment of the vascular and inflammatory complications of diabetes Trends Endocrinol Metab 11 368–375 Occurrence Handle11042467 Occurrence Handle10.1016/S1043-2760(00)00311-8 Occurrence Handle1:CAS:528:DC%2BD3cXotVSrsbY%3D

    Article  PubMed  CAS  Google Scholar 

  • AM Schmidt SD Yan SF Yan DM Stern (2001) ArticleTitleThe multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses J Clin Invest 108 949–955 Occurrence Handle11581294 Occurrence Handle1:CAS:528:DC%2BD3MXnt1Cku7k%3D

    PubMed  CAS  Google Scholar 

  • BS Szwergold S Howell PJ Beisswengen (2001) ArticleTitleHuman fructosamine-3-kinase: purification, sequencing, substrate specificity, and evidence of activity in vivo Diabetes 50 2139–2147 Occurrence Handle11522682 Occurrence Handle10.2337/diabetes.50.9.2139 Occurrence Handle1:CAS:528:DC%2BD3MXmsFKnsL0%3D

    Article  PubMed  CAS  Google Scholar 

  • M Takahashi M Pischetsrieder VM Monnier (1997) ArticleTitleMolecular cloning and expression of amadoriase isoenzyme (fructosyl amine:oxygen oxidoreductase, EC 1.5.3) from Aspergillus fumigatus J Biol Chem 272 12505–12507 Occurrence Handle9139700 Occurrence Handle10.1074/jbc.272.19.12505 Occurrence Handle1:CAS:528:DyaK2sXjtFyks7c%3D

    Article  PubMed  CAS  Google Scholar 

  • M Takeuchi S Kikuchi N Sasaki T Suzuki T Watai M Iwaki R Bucala S Yamagishi (2004) ArticleTitleInvolvement of advanced glycation end-products (AGEs) in Alzheimer’s disease Curr Alzheimer Res 1 3946 Occurrence Handle10.2174/1567205043480582

    Article  Google Scholar 

  • F Tessier M Obrenovich VM Monnier (1999) ArticleTitleStructure and mechanism of formation of human lens fluorophore LM-1. Relationship to vesperlysine A and the advanced Maillard reaction in aging, diabetes, and cataractogenesis J Biol Chem 274 20796–20804 Occurrence Handle10409619 Occurrence Handle10.1074/jbc.274.30.20796 Occurrence Handle1:CAS:528:DyaK1MXkvVKktbc%3D

    Article  PubMed  CAS  Google Scholar 

  • PJ Thornalley (2003) ArticleTitleGlyoxalase I – structure, function and a critical role in the enzymatic defence against glycation Biochem Soc Trans 31 1343–1348 Occurrence Handle14641060 Occurrence Handle1:CAS:528:DC%2BD3sXps12jtrw%3D

    PubMed  CAS  Google Scholar 

  • P Thornalley S Wolff J Crabbe A Stern (1984) ArticleTitleThe autoxidation of glyceraldehyde and other simple monosaccharides under physiological conditions catalysed by buffer ions Biochim Biophys Acta 797 276–287 Occurrence Handle6365176 Occurrence Handle1:CAS:528:DyaL2cXhtFKktr0%3D

    PubMed  CAS  Google Scholar 

  • PJ Thornalley A Langborg HS Minhas (1999) ArticleTitleFormation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucose Biochem J 344 109–116 Occurrence Handle10548540 Occurrence Handle10.1042/0264-6021:3440109 Occurrence Handle1:CAS:528:DyaK1MXns1yjtrY%3D

    Article  PubMed  CAS  Google Scholar 

  • T Usui K Shimohira H Watanabe F Hayase (2007) ArticleTitleDetection and determination of glyceraldehyde-derived pyridinium-type advanced glycation end product in streptozotocin-induced diabetic rats Biosci Biotechnol Biochem 71 442–448 Occurrence Handle17284838 Occurrence Handle10.1271/bbb.60497 Occurrence Handle1:CAS:528:DC%2BD2sXivV2it7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • F Van Herreweghe J Mao FW Chaplen J Grooten K Gevaert J Vandekerckhove K Vancompermolle (2002) ArticleTitleTumor necrosis factor-induced modulation of glyoxalase I activities through phosphorylation by PKA results in cell death and is accompanied by the formation of a specific methylglyoxal-derived AGE Proc Natl Acad Sci USA 99 949–954 Occurrence Handle11792832 Occurrence Handle10.1073/pnas.012432399 Occurrence Handle1:CAS:528:DC%2BD38Xht1Wisbs%3D

    Article  PubMed  CAS  Google Scholar 

  • PA Voziyan B Hudson (2005) ArticleTitlePyridoxamine. The many virtues of a Maillard reaction inhibitor Ann NY Acad Sci 1043 807–816 Occurrence Handle16037308 Occurrence Handle10.1196/annals.1333.093 Occurrence Handle1:CAS:528:DC%2BD2MXpvVKqu7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • PA Voziyan RG Khalifah C Thibaudeau A Yildiz J Jacob AS Serianni B Hudson (2003) ArticleTitleModification of proteins in vitro by physiological levels of glucose. Pyridoxamine inhibits conversion of Amadori intermediate to advanced glycation end-products through binding of redox metal ions J Biol Chem 278 46616–46624 Occurrence Handle12975371 Occurrence Handle10.1074/jbc.M307155200 Occurrence Handle1:CAS:528:DC%2BD3sXovFKksr8%3D

    Article  PubMed  CAS  Google Scholar 

  • E Wiame G Delpierre F Collard E Van Schaftingen (2002) ArticleTitleIdentification of a pathway for the utilization of the Amadori product fructoselysine in Escherichia coli J Biol Chem 277 42523–42529 Occurrence Handle12147680 Occurrence Handle10.1074/jbc.M200863200 Occurrence Handle1:CAS:528:DC%2BD38Xos1ensLo%3D

    Article  PubMed  CAS  Google Scholar 

  • A Wong H-L Lüth W Deuther-Conrad S Dukic-Stefanovic J Gasic-Milenkovic T Arendt G Münch (2001) ArticleTitleAdvanced glycation endproducts co-localize with inducible nitric oxide synthase in Alzheimer disease Brain Res 920 32–40 Occurrence Handle11716809 Occurrence Handle10.1016/S0006-8993(01)02872-4 Occurrence Handle1:CAS:528:DC%2BD3MXosFKrsrY%3D

    Article  PubMed  CAS  Google Scholar 

  • Y Xu X Chen (2006) ArticleTitleGlyoxalase II, a detoxifying enzyme of glycolysis byproduct methylglyoxal and a target of p63 and p73, is a pro-survival factor of the p53 family J Biol Chem 281 26713–26702

    Google Scholar 

  • S-D Yan X Chen A-M Schmidt J Brett G Godman Y-S Zou CW Scott C Caputo T Frappier MA Smith G Perry S-H Yen D Stern (1994) ArticleTitleGlycated tau protein in Alzheimer disease: a mechanism for induction of oxidant stress Proc Natl Acad Sci USA 91 7787–7791 Occurrence Handle8052661 Occurrence Handle10.1073/pnas.91.16.7787 Occurrence Handle1:CAS:528:DyaK2cXltlWmt7k%3D

    Article  PubMed  CAS  Google Scholar 

  • BZ Yang Z Makita Y Horii S Brunelle A Cerami P Sehajpal M Suthanthiran H Vlassara (1991) ArticleTitleTwo novel rat liver membrane proteins that bind advanced glycosylation endproducts: relatioship to macrophage receptor for glucose-modified proteins J Exp Med 174 515–524 Occurrence Handle1651976 Occurrence Handle10.1084/jem.174.3.515 Occurrence Handle1:CAS:528:DyaK3MXlsFKqs74%3D

    Article  PubMed  CAS  Google Scholar 

  • DV Zyzak JM Richardson SR Thorpe JW Baynes (1995) ArticleTitleFormation of reactive intermediates from Amadori compounds under physiological conditions Arch Biochem Biophys 316 547–554 Occurrence Handle7840665 Occurrence Handle10.1006/abbi.1995.1073 Occurrence Handle1:CAS:528:DyaK2MXjsV2htL4%3D

    Article  PubMed  CAS  Google Scholar 

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  1. Dipartimento di Medicina e Oncologia Sperimentale, Sezione di Biochimica, Università di Torino, Torino, Italy

    M. A. Grillo & S. Colombatto

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  1. M. A. Grillo
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  2. S. Colombatto
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Authors’ address: Maria Angelica Grillo, Dipartimento di Medicina e Oncologia Sperimentale, Sezione di Biochimica, Universita di Torino, Via Michelangelo 27, 10126 Torino, Italy

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Grillo, M., Colombatto, S. Advanced glycation end-products (AGEs): involvement in aging and in neurodegenerative diseases. Amino Acids 35, 29–36 (2008). https://doi.org/10.1007/s00726-007-0606-0

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