Abstract
Recent studies have linked carbonyl stress to many physiological processes. Increase in the levels of carbonyl compounds, derived from both endogenous and exogenous sources, is believed to accompany normal age-related decline as well as different pathologies. Reactive carbonyl species (RCS) are capable of damaging biomolecules via their involvement in a net of nonspecific reactions. In the advanced stages of RCS metabolism, variety of poorly degraded adducts and crosslinks, collectively named advanced glycoxidation end products (AGEs), arises. They are accumulated in an age-dependent manner in different tissues and organs and can contribute to inflammatory processes. In particular, detrimental effects of the end products are realized via activation of the specific receptor for AGEs (RAGE) and RAGE-dependent inflammatory signaling cascade. Although it is unclear, whether carbonyl stress is causal for age-associated impairments or it results from age- and disease-related cell damages, increased levels of RCS and AGEs are tightly related to inflammaging, and therefore, attenuation of the RAGE signaling is suggested as an effective approach for the treatment of inflammation and age-related disorders. The question raised in this review is whether specific metabolism in the aging brain related to carbonyl/RCS/AGE/RAGE stress.
Similar content being viewed by others
Abbreviations
- AGEs:
-
Advanced glycoxidation end products
- RAGE:
-
Receptor for AGEs
- RCS:
-
Reactive carbonyl species
- ROS:
-
Reactive oxygen species
References
Ahmad S, Shahab U, Baig MH, Khan MS, Khan MS, Srivastava AK, Saeed M, Moinuddin (2013) Inhibitory effect of metformin and pyridoxamine in the formation of early, intermediate and advanced glycation end-products. PLoS One 8(9):e72128. https://doi.org/10.1371/journal.pone.0072128
Ahmed N, Ahmed U, Thornalley PJ, Hager K, Fleischer G, Münch G (2005) Protein glycation, oxidation and nitration adduct residues and free adducts of cerebrospinal fluid in Alzheimer’s disease and link to cognitive impairment. J Neurochem 92(2):255–263. https://doi.org/10.1111/j.1471-4159.2004.02864.x
Aragno M, Mastrocola R (2017) Dietary sugars and endogenous formation of advanced glycation endproducts: emerging mechanisms of disease. Nutrients 9(4):385. https://doi.org/10.3390/nu9040385
Banks WA (2009) Characteristics of compounds that cross the blood-brain barrier. BMC Neurol 9(Suppl 1):S3. https://doi.org/10.1186/1471-2377-9-S1-S3
Beeri MS, Moshier E, Schmeidler J, Godbold J, Uribarri J, Reddy S, Sano M, Grossman HT, Cai W, Vlassara H, Silverman JM (2011) Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals. Mech Ageing Dev 132(11-12):583–587. https://doi.org/10.1016/j.mad.2011.10.007
Bongarzone S, Savickas V, Luzi F, Gee AD (2017) Targeting the receptor for advanced glycation endproducts (RAGE): a medicinal chemistry perspective. J Med Chem 60(17):7213–7232. https://doi.org/10.1021/acs.jmedchem.7b00058
Bruce KD, Zsombok A, Eckel RH (2017) Lipid processing in the brain: a key regulator of systemic metabolism. Front Endocrinol (Lausanne) 8:60. https://doi.org/10.3389/fendo.2017.00060
Bunn HF, Higgins PJ (1981) Reaction of monosaccharides with proteins: possible evolutionary significance. Science 213(4504):222–224. https://doi.org/10.1126/science.12192669
Castellano CA, Hudon C, Croteau E, Fortier M, St-Pierre V, Vandenberghe C, Nugent S, Tremblay S, Paquet N, Lepage M, Fülöp T, Turcotte ÉE, Dionne IJ, Potvin O, Duchesne S, Cunnane SC (2019) Links between metabolic and structural changes in the brain of cognitively normal older adults: a 4-year longitudinal follow-up. Front Aging Neurosci11:15. https://doi.org/10.3389/fnagi.2019.00015
Chambers A, Bury JJ, Minett T, Richardson CD, Brayne C, Ince PG, Shaw PJ, Garwood CJ, Heath PR, Simpson JE, Matthews FE, Wharton SB (2020) Advanced glycation end product formation in human cerebral cortex increases with Alzheimer-type neuropathologic changes but is not independently associated with dementia in a population-derived aging brain cohort. J Neuropathol Exp Neurol 79(9):950–958. https://doi.org/10.1093/jnen/nlaa064
Chen GF, Xu TH, Yan Y, Zhou YR, Jiang Y, Melcher K, Xu HE (2017) Amyloid beta: structure, biology and structure-based therapeutic development. Acta Pharmacol Sin 38(9):1205–1235. https://doi.org/10.1038/aps.2017.28
Chuah YK, Basir R, Talib H, Tie TH, Nordin N (2013) Receptor for advanced glycation end products and its involvement in inflammatory diseases. Int J Inflamm 2013:403460. 10.1155/2013/403460, 15
Chung MM, Nicol CJ, Cheng YC, Lin KH, Chen YL, Pei D, Lin CH, Shih YN, Yen CH, Chen SJ, Huang RN, Chiang MC (2017) Metformin activation of AMPK suppresses AGE-induced inflammatory response in hNSCs. Exp Cell Res 352(1):75–83. https://doi.org/10.1016/j.yexcr.2017.01.017
Croteau E, Castellano CA, Fortier M, Bocti C, Fulop T, Paquet N, Cunnane SC (2018) A cross-sectional comparison of brain glucose and ketone metabolism in cognitively healthy older adults, mild cognitive impairment and early Alzheimer’s disease. Exp Gerontol 107:18–26. https://doi.org/10.1016/j.exger.2017.07.004
Cunnane S, Nugent S, Roy M, Courchesne-Loyer A, Croteau E, Tremblay S, Castellano A, Pifferi F, Bocti C, Paquet N, Begdouri H, Bentourkia M, Turcotte E, Allard M, Barberger-Gateau P, Fulop T, Rapoport SI (2011) Brain fuel metabolism, aging, and Alzheimer’s disease. Nutrition 27(1):3–20. https://doi.org/10.1016/j.nut.2010.07.021
Deane R, Du Yan S, Submamaryan RK, LaRue B, Jovanovic S, Hogg E, Welch D, Manness L, Lin C, Yu J, Zhu H, Ghiso J, Frangione B, Stern A, Schmidt AM, Armstrong DL, Arnold B, Liliensiek B, Nawroth P, Hofman F, Kindy M, Stern D, Zlokovic B (2003) RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat Med 9(7):907-913. https://doi.org/10.1038/nm890
Dedkova EN, Blatter LA (2014) Role of β-hydroxybutyrate, its polymer poly-β-hydroxybutyrate and inorganic polyphosphate in mammalian health and disease. Front Physiol 5:260. https://doi.org/10.3389/fphys.2014.00260
Derk J, MacLean M, Juranek J, Schmidt AM (2018) The receptor for advanced glycation endproducts (RAGE) and mediation of inflammatory neurodegeneration. J Alzheimers Dis Parkinsonism 8(1):421. https://doi.org/10.4172/2161-0460.1000421
Dienel GA (2019) Brain glucose metabolism: integration of energetics with function. Physiol Rev 99(1):949–1045. https://doi.org/10.1152/physrev.00062.2017
Ding Q, Keller JN (2005) Evaluation of rage isoforms, ligands, and signaling in the brain. Biochim Biophys Acta 1746(1):18–27. https://doi.org/10.1016/j.bbamcr.2005.08.006
Doens D, Fernández PL (2014) Microglia receptors and their implications in the response to amyloid β for Alzheimer’s disease pathogenesis. J Neuroinflammation 11:48. https://doi.org/10.1186/1742-2094-11-48
Dyer DG, Blackledge JA, Katz BM, Hull CJ, Adkisson HD, Thorpe SR, Lyons TJ, Baynes JW (1991) The Maillard reaction in vivo. Z Ernahrungswiss 30(1):29–45. https://doi.org/10.1007/BF01910730
Egaña-Gorroño L, López-Díez R, Yepuri G, Ramirez LS, Reverdatto S, Gugger PF, Shekhtman A, Ramasamy R, Schmidt AM (2020) Receptor for advanced glycation end products (RAGE) and mechanisms and therapeutic opportunities in diabetes and cardiovascular disease: insights from human subjects and animal models. Front Cardiovasc Med 7:37. https://doi.org/10.3389/fcvm.2020.00037
Ellis EM (2007) Reactive carbonyls and oxidative stress: potential for therapeutic intervention. Pharmacol Ther 115(1):13–24. https://doi.org/10.1016/j.pharmthera.2007.03.015
Emanuele E, D’Angelo A, Tomaino C, Binetti G, Ghidoni R, Politi P, Bernardi L, Maletta R, Bruni AC, Geroldi D (2005) Circulating levels of soluble receptor for advanced glycation end products in Alzheimer disease and vascular dementia. Arch Neurol 62(11):1734–1736. https://doi.org/10.1001/archneur.62.11.1734
Evans M, Cogan KE, Egan B (2017) Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation. J Physiol 595(9):2857–2871. https://doi.org/10.1113/JP273185
Falone S, D’Alessandro A, Mirabilio A, Petruccelli G, Cacchio M, Di Ilio C, Di Loreto S, Amicarelli F (2012) Long term running biphasically improves methylglyoxal-related metabolism, redox homeostasis and neurotrophic support within adult mouse brain cortex. PLoS ONE 7(2):e31401. https://doi.org/10.1371/journal.pone.0031401
Fioramonti X, Pénicaud L (2019) Carbohydrates and the brain: roles and impact. In: Bosch-Bouju C, Layé S, Pallet V (eds) Feed your mind - How does nutrition modulate brain function throughout life? IntechOpen, London, UK, pp 386–390. https://doi.org/10.5772/intechopen.88366
Flanagan E, Lamport D, Brennan L, Burnet P, Calabrese V, Cunnane SC, de Wilde MC, Dye L, Farrimond JA, Emerson Lombardo N, Hartmann T, Hartung T, Kalliomäki M, Kuhnle GG, La Fata G, Sala-Vila A, Samieri C, Smith AD, Spencer JPE, Thuret S, Tuohy K, Turroni S, Vanden Berghe W, Verkuijl M, Verzijden K, Yannakoulia M, Geurts L, Vauzour D (2020) Nutrition and the ageing brain: moving towards clinical applications. Ageing Res Rev 62:101079. https://doi.org/10.1016/j.arr.2020.101079
Foretz M, Guigas B, Bertrand L, Pollak M, Viollet B (2014) Metformin: from mechanisms of action to therapies. Cell Metab 20(6):953–966. https://doi.org/10.1016/j.cmet.2014.09.018
Forman HJ, Fukuto JM, Miller T, Zhang H, Rinna A, Levy S (2008) The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal. Arch Biochem Biophys 477(2):183–195. https://doi.org/10.1016/j.abb.2008.06.011
Fuller S, Münch G, Steele M (2009) Activated astrocytes: a therapeutic target in Alzheimer’s disease? Expert Rev Neurother 9:1585–1594. https://doi.org/10.1586/ern.09.111
Garaschuk O, Semchyshyn HM, Lushchak VI (2018) Healthy brain aging: Interplay between reactive species, inflammation and energy supply. Ageing Res Rev 43:26–45. https://doi.org/10.1016/j.arr.2018.02.003
Gaut JP, Yeh GC, Tran HD, Byun J, Henderson JP, Richter GM, Brennan ML, Lusis AJ, Belaaouaj A, Hotchkiss RS, Heinecke JW (2001) Neutrophils employ the myeloperoxidase system to generate antimicrobial brominating and chlorinating oxidants during sepsis. Proc Natl Acad Sci USA 98(21):11961–11966. https://doi.org/10.1073/pnas.211190298
Gilad GM, Gilad VH (2003) Overview of the brain polyamine-stress-response: regulation, development, and modulation by lithium and role in cell survival. Cell Mol Neurobiol 23(4-5):637–649. https://doi.org/10.1023/a:1025036532672
Green PS, Mendez AJ, Jacob JS, Crowley JR, Growdon W, Hyman BT, Heinecke JW (2004) Neuronal expression of myeloperoxidase is increased in Alzheimer’s disease. J Neurochem 90(3):724–733. https://doi.org/10.1111/j.1471-4159.2004.02527.x
Grillo MA, Colombatto S (2008) Advanced glycation end-products (AGEs): involvement in aging and in neurodegenerative diseases. Amino Acids 35(1):29–36. https://doi.org/10.1007/s00726-007-0606-0
Gu Q, Wang B, Zhang X-F, Ma Y-P, Liu J-D, Wang X-Z (2014) Contribution of receptor for advanced glycation end products to vasculature-protecting effects of exercise training in aged rats. Eur J Pharmacol 741:186–194. https://doi.org/10.1016/j.ejphar.2014.08.017
Halliwell B, Gutteridge JMC (1989) Free radicals in biology and medicine, 2nd edn. Clarendon Press, Oxford, UK
Hayward LD, Angyal SJ (1977) A symmetry rule for the circular dichroism of reducing sugars, and the proportion of carbonyl forms in aqueous solutions thereof. Carbohydr Res 53:13–20. https://doi.org/10.1016/S0008-6215(00)85450-6
He CJ, Koschinsky T, Buenting C, Vlassara H (2001) Presence of diabetic complications in type 1 diabetic patients correlates with low expression of mononuclear cell AGE-receptor-1 and elevated serum AGE. Mol Med 7(03):159–168
Hwang JJ, Jiang L, Hamza M, Dai F, Belfort-DeAguiar R, Cline G, Rothman DL, Mason G, Sherwin RS (2017) The human brain produces fructose from glucose. JCI Insight 2(4):e90508. https://doi.org/10.1172/jci.insight.90508
Iłzecka J (2009) Serum-soluble receptor for advanced glycation end product levels in patients with amyotrophic lateral sclerosis. Acta Neurol Scand 120(2):119–122. https://doi.org/10.1111/j.1600-0404.2008.01133.x
Jacobs AT, Marnett LJ (2010) Systems analysis of protein modification and cellular responses induced by electrophile stress. Acc Chem Res 43(5):673–683. https://doi.org/10.1021/ar900286y
Joffre C (2019) Polyunsaturated fatty acid metabolism in the brain and brain cells. In: Bosch-Bouju C, Layé S, Pallet V (eds) Feed your mind - How does nutrition modulate brain function throughout life? IntechOpen, London, UK, pp 13–36. https://doi.org/10.5772/intechopen.88232
Jové M, Pradas I, Dominguez-Gonzalez M, Ferrer I, Pamplona R (2019) Lipids and lipoxidation in human brain aging. Mitochondrial ATP-synthase as a key lipoxidation target. Redox. Biol 23:101082. https://doi.org/10.1016/j.redox.2018.101082
Juranek JK, Daffu GK, Wojtkiewicz J, Lacomis D, Kofler J, Schmidt AM (2015) Receptor for advanced glycation end products and its inflammatory ligands are upregulated in amyotrophic lateral sclerosis. Front Cell Neurosci 9:485. https://doi.org/10.3389/fncel.2015.00485
Kalapos MP (2008) Methylglyoxal and glucose metabolism: a historical perspective and future avenues for research. Drug Metabol Drug Interact 23(1-2):69–91. https://doi.org/10.1515/dmdi.2008.23.1-2.69
Kalapos MP (2013) Where does plasma methylglyoxal originate from? Diabetes Res Clin Pract 99(3):260–271. https://doi.org/10.1016/j.diabres.2012.11.003
Kalea AZ, Schmidt AM, Hudson BI (2011) Alternative splicing of RAGE: roles in biology and disease. Front Biosci (Landmark Ed) 16:2756–2770. https://doi.org/10.2741/3884
Keller JN, Schmitt FA, Scheff SW, Ding Q, Chen Q, Butterfield DA, Markesbery WR (2005) Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology 64(7):1152–1156. https://doi.org/10.1212/01.WNL.0000156156.13641.BA
Kierdorf K, Fritz G (2013) RAGE regulation and signaling in inflammation and beyond. J Leukoc Biol 94(1):55–68. https://doi.org/10.1189/jlb.1012519
Kikuchi S, Shinpo K, Takeuchi M, Yamagishi S, Makita Z, Sasaki N, Tashiro K (2003) Glycation—a sweet tempter for neuronal death. Brain Res Rev 41(2-3):306–323. https://doi.org/10.1016/s0165-0173(02)00273-4
Kimura T, Takamatsu J, Araki N, Goto M, Kondo A, Miyakawa T, Horiuchi S (1995) Are advanced glycation end-products associated with amyloidosis in Alzheimer’s disease? Neuroreport 6(6):866–868. https://doi.org/10.1097/00001756-199504190-00010
Koch M, Chitayat S, Dattilo BM, Schiefner A, Diez J, Chazin WJ, Fritz G (2010) Structural basis for ligand recognition and activation of RAGE. Structure 18(10):1342–1352. https://doi.org/10.1016/j.str.2010.05.017
Krautwald M, Münch G (2010) Advanced glycation end products as biomarkers and gerontotoxins—a basis to explore methylglyoxal-lowering agents for Alzheimer’s disease? Exp Gerontol 45(10):744–751. https://doi.org/10.1016/j.exger.2010.03.001
Kuhla B, Boeck K, Lüth HJ, Schmidt A, Weigle B, Schmitz M, Ogunlade V, Münch G, Arendt T (2006) Age-dependent changes of glyoxalase I expression in human brain. Neurobiol Aging 27(6):815–822. https://doi.org/10.1016/j.neurobiolaging.2005.04.006
Kuhla B, Boeck K, Schmidt A, Ogunlade V, Arendt T, Münch G, Lüth HJ (2007) Age- and stage-dependent glyoxalase I expression and its activity in normal and Alzheimer’s disease brains. Neurobiol Aging 28(1):29–41. https://doi.org/10.1016/j.neurobiolaging.2005.11.007
Lai AY, McLaurin J (2010) Mechanisms of amyloid-beta peptide uptake by neurons: the role of lipid rafts and lipid raft-associated proteins. Int J Alzheimers Dis 2011 11:548380. https://doi.org/10.4061/2011/548380
Lanati N, Emanuele E, Brondino N, Geroldi D (2010) Soluble RAGE-modulating drugs: state-of-the-art and future perspectives for targeting vascular inflammation. Curr Vasc Pharmacol 8(1):86–92. https://doi.org/10.2174/157016110790226642
Lee S, Piao C, Kim G, Kim JY, Choi E, Lee M (2018) Production and application of HMGB1 derived recombinant RAGE-antagonist peptide for anti-inflammatory therapy in acute lung injury. Eur J Pharm Sci 114:275–284. https://doi.org/10.1016/j.ejps.2017.12.019
Lerdkrai C, Asavapanumas N, Brawek B, Kovalchuk Y, Mojtahedi N, Olmedillas Del Moral M, Garaschuk O (2018) Intracellular Ca2+ stores control in vivo neuronal hyperactivity in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci U S A 115(6):E1279–E1288. https://doi.org/10.1073/pnas.1714409115
Limanaqi F, Biagioni F, Gambardella S, Familiari P, Frati A, Fornai F (2020) Promiscuous roles of autophagy and proteasome in neurodegenerative proteinopathies. Int J Mol Sci 21(8):3028. https://doi.org/10.3390/ijms21083028
Lin AL, Zhang W, Gao X, Watts L (2015) Caloric restriction increases ketone bodies metabolism and preserves blood flow in aging brain. Neurobiol Aging 36(7):2296–2303. https://doi.org/10.1016/j.neurobiolaging.2015.03.012
Loeffler DA (2019) Influence of normal aging on brain autophagy: a complex scenario. Front Aging Neurosci 11:49. https://doi.org/10.3389/fnagi.2019.00049
Loving BA, Bruce KD (2020) Lipid and lipoprotein metabolism in microglia. Front Physiol 11:393. https://doi.org/10.3389/fphys.2020.00393
Lu M, Chen H, Nie F, Wei X, Tao Z, Ma J (2020) The potential role of metformin in the treatment of Parkinson’s disease. Journal of Bio-X Research 3(1):27–35. https://doi.org/10.1097/JBR.0000000000000055
Lue L-F, Walker DG, Jacobson S, Sabbagh M (2009) Receptor for advanced glycation end products its role in Alzheimer’s disease and other neurological diseases. Future Neurol 4(2):167–177. https://doi.org/10.2217/14796708.4.2.167
Lushchak VI (2014) Free radicals, reactive oxygen species, oxidative stress and its classification. Chem Biol Interact 224:164–175. https://doi.org/10.1016/j.cbi.2014.10.016
MacLean M, Derk J, Ruiz HH, Juranek JK, Ramasamy R, Schmidt AM (2019) The receptor for advanced glycation end products (RAGE) and DIAPH1: implications for vascular and neuroinflammatory dysfunction in disorders of the central nervous system. Neurochem Int 126:154–164. https://doi.org/10.1016/j.neuint.2019.03.012
Markowicz-Piasecka M, Sikora J, Szydłowska A, Skupień A, Mikiciuk-Olasik E, Huttunen KM (2017) Metformin—a future therapy for neurodegenerative diseases: Theme: Drug discovery, development and delivery in Alzheimer’s disease guest editor: Davide Brambilla. Pharm Res 34(12):2614–2627. https://doi.org/10.1007/s11095-017-2199-y
Martins AM, Cordeiro CA, Ponces Freire AM (2001) In situ analysis of methylglyoxal metabolism in Saccharomyces cerevisiae. FEBS Lett 499(1-2):41–44. https://doi.org/10.1016/S0014-5793(01)02519-4
McAllister MJ, Waldman HS, Rentería LI, Gonzalez AE, Butawan MB, Bloomer RJ (2020) Acute coffee ingestion with and without medium-chain triglycerides decreases blood oxidative stress markers and increases ketone levels. Can J Physiol Pharmacol 98(4):194–200. https://doi.org/10.1139/cjpp-2019-0458
Mergenthaler P, Lindauer U, Dienel GA, Meisel A (2013) Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends Neurosci 36(10):587–597. https://doi.org/10.1016/j.tins.2013.07.001
Miyata T, van Ypersele de Strihou C, Kurokawa K, Baynes JW (1999) Alterations in nonenzymatic biochemistry in uremia: origin and significance of “carbonyl stress” in long-term uremic complications. Kidney Int 55:389–399. https://doi.org/10.1046/j.1523-1755.1999.00302.x
Miyazaki A, Nakayama H, Horiuchi S (2002) Scavenger receptors that recognize advanced glycation end products. Trends Cardiovasc Med 12(6):258–262. https://doi.org/10.1016/s1050-1738(02)00171-8
Mol M, Degani G, Coppa C, Baron G, Popolo L, Carini M, Aldini G, Vistoli G, Altomare A (2019) Advanced lipoxidation end products (ALEs) as RAGE binders: mass spectrometric and computational studies to explain the reasons why. Redox Biol 23:101083. https://doi.org/10.1016/j.redox.2018.101083
Monnier VM, Cerami A (1981) Nonenzymatic browning in vivo: possible process for aging of long-lived proteins. Science 211(4481):491–493. https://doi.org/10.1126/science.6779377
Mosconi L (2013) Glucose metabolism in normal aging and Alzheimer’s disease: methodological and physiological considerations for PET studies. Clin Transl Imaging 1(4). http://doi.org/10.1007/s40336-013-0026-y, 217, 233
Münch G, Shepherd CE, McCann H, Brooks WS, Kwok JB, Arendt T, Hallupp M, Schofield PR, Martins RN, Halliday GM (2002) Intraneuronal advanced glycation endproducts in presenilin-1 Alzheimer’s disease. Neuroreport 13(5):601–604. https://doi.org/10.1097/00001756-200204160-00013
Neal EG, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G, Whitney A, Cross JH (2009) A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsy. Epilepsia 50:1109–1117. https://doi.org/10.1111/j.1528-1167.2008.01870.x
Niki E (2009) Lipid peroxidation: physiological levels and dual biological effects. Free Radic Biol Med 47(5):469–484. https://doi.org/10.1016/j.freeradbiomed.2009.05.032
Norman JE, Rutkowsky J, Bodine S, Rutledge JC (2018) The potential mechanisms of exercise-induced cognitive protection: a literature review. Curr Pharm Des 24(17):1827–1831. https://doi.org/10.2174/1381612824666180406105149
O’Brien PJ, Siraki AG, Shangari N (2005) Aldehyde sources, metabolism, molecular toxicity mechanisms, and possible effects on human health. Crit Rev Toxicol 35(7):609–662. https://doi.org/10.1080/10408440591002183
Olmedillas Del Moral M, Asavapanumas N, Uzcátegui NL, Garaschuk O (2019) Healthy brain aging modifies microglial calcium signaling in vivo. Int J Mol Sci 20(3):589. https://doi.org/10.3390/ijms20030589
Olmedillas Del Moral M, Fröhlich N, Figarella K, Mojtahedi N, Garaschuk O (2020) Effect of caloric restriction on the in vivo functional properties of aging microglia. Front Immunol 11:750. https://doi.org/10.3389/fimmu.2020.00750
Ott C, Jacobs K, Haucke E, Navarrete Santos A, Grune T, Simm A (2014) Role of advanced glycation end products in cellular signaling. Redox Biol 2:411–429. https://doi.org/10.1016/j.redox.2013.12.016
Pamplona R (2011) Advanced lipoxidation end-products. Chem Biol Interact 192(1-2):14–20. https://doi.org/10.1016/j.cbi.2011.01.007
Park H, Adsit FG, Boyington JC (2010) The 1.5 Å crystal structure of human receptor for advanced glycation endproducts (RAGE) ectodomains reveals unique features determining ligand binding. J Biol Chem 285:40762–40770. https://doi.org/10.1074/jbc.M110.169276
Peng X, Ma J, Chen F, Wang M (2011) Naturally occurring inhibitors against the formation of advanced glycation end-products. Food Funct 2(6):289–301. https://doi.org/10.1039/c1fo10034c
Picklo MJ, Olson SJ, Markesbery WR, Montine TJ (2001) Expression and activities of aldo-keto oxidoreductases in Alzheimer disease. J Neuropathol Exp Neurol 60(7):686–695. https://doi.org/10.1093/jnen/60.7.686
Ping F, Jiang N, Yu L (2020) Association between metformin and neurodegenerative diseases of observational studies: systematic review and meta-analysis. BMJ Open Diabetes Res Care 8(1):e001370. https://doi.org/10.1136/bmjdrc-2020-001370
Poulsen MW, Hedegaard RV, Andersen JM, de Courten B, Bügel S, Nielsen J, Skibsted LH, Dragsted LO (2013) Advanced glycation endproducts in food and their effects on health. Food Chem Toxicol 60:10-37. https://doi.org/10.1016/j.fct.2013.06.052
Prasad K (2014) Low levels of serum soluble receptors for advanced glycation end products, biomarkers for disease state: myth or reality. Int J Angiol 23(1):11–16. https://doi.org/10.1055/s-0033-1363423
Prasad K (2019) Is there any evidence that AGE/sRAGE is a universal biomarker/risk marker for diseases? Mol Cell Biochem 451(1-2):139–144. https://doi.org/10.1007/s11010-018-3400-2
Prasad K, Mishra M (2018) AGE-RAGE stress, stressors, and antistressors in health and disease. Int J Angiol 27(1):1–12. https://doi.org/10.1055/s-0037-1613678
Prasad C, Davis KE, Imrhan V, Juma S, Vijayagopal P (2017) Advanced glycation end products and risks for chronic diseases: intervening through lifestyle modification. Am J Lifestyle Med 13(4):384–404. https://doi.org/10.1177/1559827617708991
Puchalska P, Crawford PA (2017) Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics. Cell Metab 25:262–284. https://doi.org/10.1016/j.cmet.2016.12.022
Ramasamy R, Vannucci SJ, Yan SS, Herold K, Yan SF, Schmidt AM (2005) Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. Glycobiology 15(7):16R–28R. https://doi.org/10.1093/glycob/cwi053
Ramirez AI, de Hoz R, Salobrar-Garcia E, Salazar JJ, Rojas B, Ajoy D, López-Cuenca I, Rojas P, Triviño A, Ramírez JM (2017) The role of microglia in retinal neurodegeneration: Alzheimer’s disease, Parkinson, and glaucoma. Front Aging Neurosci 9:214. https://doi.org/10.3389/fnagi.2017.00214
Rena G, Hardie DG, Pearson ER (2017) The mechanisms of action of metformin. Diabetologia 60(9):1577–1585. https://doi.org/10.1007/s00125-017-4342-z
Robert L, Labat-Robert J, Robert AM (2010) The Maillard reaction. From nutritional problems to preventive medicine. Pathol Biol (Paris) 58(3):200–206. https://doi.org/10.1016/j.patbio.2009.09.004
Roher AE, Esh CL, Kokjohn TA, Castaño EM, Van Vickle GD, Kalback WM, Patton RL, Luehrs DC, Daugs ID, Kuo YM, Emmerling MR, Soares H, Quinn JF, Kaye J, Connor DJ, Silverberg NB, Adler CH, Seward JD, Beach TG, Sabbagh MN (2009) Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer’s disease. Alzheimers Dement 5(1):18-29. https://doi.org/10.1016/j.jalz.2008.10.004
Rowan S, Bejarano E, Taylor A (2018) Mechanistic targeting of advanced glycation end-products in age-related diseases. Biochim Biophys Acta Mol Basis Dis 1864(12):3631–3643. https://doi.org/10.1016/j.bbadis.2018.08.036
Sakai M, Oimomi M, Kasuga M (2002) Experimental studies on the role of fructose in the development of diabetic complications. Kobe J Med Sci 48(5-6):125–136
Schaur RJ, Siems W, Bresgen N, Eckl PM (2015) 4-Hydroxy-nonenal—a bioactive lipid peroxidation product. Biomolecules 5:2247–2337. https://doi.org/10.3390/biom5042247
Schmidt AM, Vianna M, Gerlach M, Brett J, Ryan J, Kao J, Esposito C, Hegarty H, Hurley W, Clauss M, Wang F, Panll Y-CE, Tsang TC, Stern D (1992) Isolation and characterization of two binding proteins for advanced glycosylation end products from bovine lung which are present on the endothelial cell surface. J Biol Chem 267:14987–14997
Semchyshyn H (2018) Is part of the fructose effects on health related to increased AGE formation? In: Uribarri J (ed) Dietary AGEs and Their Role in Health and Disease. CRC Press Taylor & Francis Group, pp 103–111
Semchyshyn H, Lozinska L (2012) Fructose protects baker’s yeast against peroxide stress: potential role of catalase and superoxide dismutase. FEMS Yeast Res 12(7):761–773. https://doi.org/10.1111/j.1567-1364.2012.00826.x
Semchyshyn H, Miedzobrodzki J, Bayliak M, Lozinska L, Homza B (2014) Fructose compared with glucose is more a potent glycoxidation agent in vitro, but not under carbohydrate-induced stress in vivo: potential role of antioxidant and antiglycation enzymes. Carbohydr Res 384:61–69. https://doi.org/10.1016/j.carres.2013.11.015
Semchyshyn HM (2014) Reactive carbonyl species in vivo: generation and dual biological effects. Sci World J 10:417842. https://doi.org/10.1155/2014/417842
Semchyshyn HM, Lozinska LM, Miedzobrodzki J, Lushchak VI (2011) Fructose and glucose differentially affect aging and carbonyl/oxidative stress parameters in Saccharomyces cerevisiae cells. Carbohydr Res 346(7):933–938. https://doi.org/10.1016/j.carres.2011.03.005
Semchyshyn HM, Lushchak VI (2012) Interplay between oxidative and carbonyl stresses: molecular mechanisms, biological effects and therapeutic strategies of protection. In: Lushchak VI, Semchyshyn HM (eds) Oxidative stress – Molecular mechanisms and biological effects. InTech, Rijeka, Croatia, pp 15–46
Senatus LM, Schmidt AM (2017) The AGE-RAGE axis: Implications for age-associated arterial diseases. Front Genet 8:187. https://doi.org/10.3389/fgene.2017.00187
Shimizu Y, Harashima A, Munesue S, Oishi M, Hattori T, Hori O, Kitao Y, Yamamoto H, Leerach N, Nakada M, Yamamoto Y, Hayashi Y (2020) Neuroprotective effects of endogenous secretory receptor for advanced glycation end-products in brain ischemia. Aging Dis 11(3):547–558. https://doi.org/10.14336/AD.2019.0715
Sitkiewicz E, Tarnowski K, Poznański J, Kulma M, Dadlez M (2013) Oligomerization interface of RAGE receptor revealed by MS-monitored hydrogen deuterium exchange. PLoS One 8(10):e76353. https://doi.org/10.1371/journal.pone.0076353
Sorci G, Riuzzi F, Giambanco I, Donato R (2013) RAGE in tissue homeostasis, repair and regeneration. Biochim Biophys Acta 1833(1):101–109. https://doi.org/10.1016/j.bbamcr.2012.10.021
Sourris KC, Harcourt BE, Penfold SA, Yap FY, Morley AL, Morgan PE, Davies MJ, Baker ST, Jerums G, Forbes JM (2010) Modulation of the cellular expression of circulating advanced glycation end-product receptors in type 2 diabetic nephropathy. Exp Diabetes Res 2010 9:974681. https://doi.org/10.1155/2010/974681
Sparvero LJ, Asafu-Adjei D, Kang R, Tang D, Amin N, Im J, Rutledge R, Lin B, Amoscato AA, Zeh HJ, Lotze MT (2009) RAGE (Receptor for Advanced Glycation Endproducts) RAGE ligands, and their role in cancer and inflammation. J Transl Med 7:17. https://doi.org/10.1186/1479-5876-7-17
Sternberg Z, Weinstock-Guttman B, Hojnacki D, Zamboni P, Zivadinov R, Chadha K, Lieberman A, Kazim L, Drake A, Rocco P, Grazioli E, Munschauer F (2008) Soluble receptor for advanced glycation end products in multiple sclerosis: a potential marker of disease severity. Mult Scler 14(6):759–763. https://doi.org/10.1177/1352458507088105
Takeda M, Ohnuma T, Takeuchi M, Katsuta N, Maeshima H, Takebayashi Y, Higa M, Nakamura T, Nishimon S, Sannohe T, Hotta Y, Hanzawa R, Higashiyama R, Shibata N, Gohda T, Suzuki Y, Yamagishi S, Tomino Y, Arai H (2015) Altered serum glyceraldehyde-derived advanced glycation end product (AGE) and soluble AGE receptor levels indicate carbonyl stress in patients with schizophrenia. Neurosci Lett 593:51–55. https://doi.org/10.1016/j.neulet.2015.03.002
Takeuchi M, Bucala R, Suzuki T, Ohkubo T, Yamazaki M, Koike T, Kameda Y, Makita Z (2000) Neurotoxicity of advanced glycation end-products for cultured cortical neurons. Neuropathol Exp Neurol 59(12):1094–1105. https://doi.org/10.1093/jnen/59.12.1094
Tamura Y, Adachi H, Osuga J, Ohashi K, Yahagi N, Sekiya M, Okazaki H, Tomita S, Iizuka Y, Shimano H, Nagai R, Kimura S, Tsujimoto M, Ishibashi S (2003) FEEL-1 and FEEL-2 are endocytic receptors for advanced glycation end products. J Biol Chem 278(15):12613–12617. https://doi.org/10.1074/jbc.M210211200
Turk Z (2010) Glycotoxines, carbonyl stress and relevance to diabetes and its complications. Physiol Res 59(2):147–156
Uchida K (2000) Role of reactive aldehyde in cardiovascular diseases. Free Radic Biol Med 28(12):1685–1696. https://doi.org/10.1016/s0891-5849(00)00226-4
Uribarri J (2018) Dietary AGEs and their role in health and disease, 1st edn. CRC Press, Taylor & Francis Group. https://doi.org/10.1201/9781315120041
Vlassara H, Brownlee M, Cerami A (1985) High-affinity-receptor-mediated uptake and degradation of glucose-modified proteins: a potential mechanism for the removal of senescent macromolecules. Proc Natl Acad Sci USA 82:5588–5592. https://doi.org/10.1073/pnas.82.17.5588
Wang WY, Tan MS, Yu JT, Tan L (2015) Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann Transl Med 3(10):136. https://doi.org/10.3978/j.issn.2305-5839.2015.03.49
Wood PL, Khan MA, Moskal JR (2007) The concept of aldehyde load in neurodegenerative mechanisms: cytotoxicity of the polyamine degradation products hydrogen peroxide, acrolein, 3-aminopropanal, 3-acetamidopropanal and 4-aminobutanal in a retinal ganglion cell line. Brain Res 1145:150–156. https://doi.org. https://doi.org/10.1016/j.brainres.2006.10.004
Wooda TR, Stubbsc BJ, Juula SE (2018) Exogenous ketone bodies as promising neuroprotective agents for developmental brain injury. Dev Neurosci 40:451–462. https://doi.org/10.1159/000499563
Xie J, Méndez JD, Méndez-Valenzuela V, Aguilar-Hernández MM (2013) Cellular signalling of the receptor for advanced glycation end products (RAGE). Cell Signal 25(11):2185–2197. https://doi.org/10.1016/j.cellsig.2013.06.013
Xu J, Begley P, Church SJ, Patassini S, McHarg S, Kureishy N, Hollywood KA, Waldvogel HJ, Liu H, Zhang S, Lin W, Herholz K, Turner C, Synek BJ, Curtis MA, Rivers-Auty J, Lawrence CB, Kellett KA, Hooper NM, Vardy ER, Wu D, Unwin RD, Faull RL, Dowsey AW, Cooper GJ (2016) Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer’s disease: metabolic basis for dementia. Sci Rep 6:27524. https://doi.org/10.1038/srep27524
Xue M, Rabbani N, Thornalley PJ (2011) Glyoxalase in ageing. Semin Cell Dev Biol 22(3):293–301. https://doi.org/10.1016/j.semcdb.2011.02.013
Zhang H, Forman HJ (2017) 4-hydroxynonenal-mediated signaling and aging. Free Radic Biol Med 111:219–225. https://doi.org/10.1016/j.freeradbiomed.2016.11.032
Zhou Z, Tang Y, Jin X, Chen C, Lu Y, Liu L, Shen C (2016) Metformin inhibits advanced glycation end products-induced inflammatory response in murine macrophages partly through AMPK activation and RAGE/NFkappaB pathway suppression. J Diabetes Res 10:4847812. https://doi.org/10.1155/2016/4847812
Zimniak P (2011) Relationship of electrophilic stress to aging. Free Radic Biol Med 51(6):1087–1105. https://doi.org/10.1016/j.freeradbiomed.2011.05.039
Acknowledgment
The author gratefully acknowledges three anonymous referees for their helpful suggestions and comments that improved the manuscript.
Funding
This work was supported by the grant from the Ministry of Education and Science of Ukraine (#0118U003477).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The author declares that she has no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the special issue on Aging Brain in Pflügers Archiv—European Journal of Physiology
Rights and permissions
About this article
Cite this article
Semchyshyn, H. Is carbonyl/AGE/RAGE stress a hallmark of the brain aging?. Pflugers Arch - Eur J Physiol 473, 723–734 (2021). https://doi.org/10.1007/s00424-021-02529-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00424-021-02529-y