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Cited by 538Alzheimer's disease research and treatmentsMitochondrial Function and PathologyNeuroinflammation and Neurodegeneration Mechanisms

Energy metabolism and inflammation in brain aging and Alzheimer’s disease

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Yin, Fei, Sancheti, Harsh, Patil, Ishan, Cadenas, Enrique·2016·Free Radical Biology and Medicine
DOI 10.1016/j.freeradbiomed.2016.04.200PMC PMC5094909
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Abstract

The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer's disease. As important cellular sources of H 2 O 2, mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer's disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer's disease. Interaction of these systems is reviewed based on basic research and clinical studies.

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  • Early-stage metabolic changes have been detected in the brains of AD patients.

    “early-stage metabolic changes have been detected in the brains of AD patients”

    From APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons (2024) · cites this paper as [8]

  • APOE plays a prominent role in the bioenergetic homeostasis of the brain.

    “APOE plays a prominent role in the bioenergetic homeostasis of the brain”

    From APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons (2024) · cites this paper as [8]

    Section 2.1 discusses brain insulin resistance as associated with Alzheimer’s disease independently of apolipoprotein E status; section 4.5 discusses APOE status in relation to neuroinflammation. Neither passage says APOE plays a prominent role in brain bioenergetic homeostasis (searched: APOE, apolipoprotein E, bioenergetic homeostasis). (LLM, conf=0.76)

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  1. [1]Imtiaz B Tolppanen AM Kivipelto M Soininen H Future directions in Alzheimer’s disease from risk factors to prevention Biochem Pharmacol 88 661 670 2014 24418410
  2. [2]Rossi S Zanier ER Mauri I Columbo A Stocchetti N Brain temperature, body core temperature, and intracranial pressure in acute cerebral damage J Neurol Neurosurg Psychiatry 71 448 454 2001 11561026 PMC1763520
  3. [3]Blass JP Sheu RK Gibson GE Inherent abnormalities in energy metabolism in Alzheimer disease. Interaction with cerebrovascular compromise Ann NY Acad Sci 903 204 221 2000 10818509
  4. [5]de la Monte S Wands J Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: relevance to Alzheimer’s disease J Alzheimers Dis 7 45 61 2005 15750214
  5. [6]Harper S Economic and social implications of aging societies Science 346 587 591 2014 25359967
  6. [7]van Heemst D Insulin, IGF-1 and longevity Aging Dis 1 147 157 2010 22396862 PMC3295030
  7. [8]Cheng Z Tseng Y White MF Insulin signaling meets mitochondria in metabolism Trends Endocrinol Metab 21 589 598 2010 20638297 PMC3994704
  8. [10]De Felice FG Ferreira ST Inflammation, defective insulin signaling, and mitochondrial dysfunction as common molecular denominators connecting type 2 diabetes to Alzheimer disease Diabetes 63 2262 2272 2014 24931033
  9. [11]Spielman LJ Little JP Klegeris A Inflammation and insulin/IGF-1 resistance as the possible link between obesity and neurodegeneration J Neuroimmunol 273 8 21 2014 24969117
  10. [12]Kapetanovic R Bokil NJ Sweet MJ Innate immune perturbations, accumulating DAMPs and inflammasome dysregulation: A ticking time bomb in ageing Ageing Res Rev 24 40 53 2015 25725308
  11. [13]Glass CK Saijo K Winner B Marchetto MC Gage FH Mechanisms underlying inflammation in neurodegeneration Cell 140 918 934 2010 20303880 PMC2873093
  12. [14]Jiang T Cadenas E Astrocytic metabolic and inflammatory changes as a function of age Aging Cell 13 1059 1067 2014 25233945 PMC4244278
  13. [15]Yin F Boveris A Cadenas E Mitochondrial energy metabolism and redox signaling in brain aging and neurodegeneration Antioxid Redox Signal 20 353 371 2014 22793257 PMC3887431
  14. [16]Yin F Sancheti H Liu Z Cadenas E Mitochondrial function in ageing: coordination with signalling and transcriptional pathways J Physiol n/a n/a 2015 PMC4933098 26293414
  15. [18]Cohen E Dillin A The insulin paradox: aging, proteotoxicity and neurodegeneration Nat Rev Neurosci 9 759 767 2008 18769445 PMC2692886
  16. [19]Yin F Jiang T Cadenas E Metabolic triad in brain aging: mitochondria, insulin/IGF-1 signalling, and JNK signalling Biochem Soc Trans 41 101 105 2013 23356266 PMC9934302
  17. [20]Csiszar A Wang M Lakatta EG Ungvari Z Inflammation and endothelial dysfunction during aging: role of NF-κB J Appl Physiol 105 1333 1341 2008 18599677 PMC2576023
  18. [22]Havrankova J Roth J Brownstein MJ Concentrations of insulin and insulin receptors in the brain are independent of peripheral insulin levels. Studies of obese and streptozotocin-treated rodents J Clin Invest 64 636 642 1979 156737 PMC372161
  19. [23]van der Heide LP Ramakers GM Smidt MP Insulin signaling in the central nervous system: learning to survive Prog Neurobiol 79 205 221 2006 16916571
  20. [24]Grillo CA Piroli GG Hendry RM Reagan LP Insulin-stimulated translocation of GLUT4 to the plasma membrane in rat hippocampus is PI3-kinase dependent Brain Res 1296 35 45 2009 19679110 PMC2997526
  21. [25]Brüning J Gautam D Burks DJ Gillette J Schubert M Orban PC Klein R Krone W Müller-Wieland D Kahn CR Role of Brain Insulin Receptor in Control of Body Weight and Reproduction Science 289 2122 2125 2000 11000114
  22. [26]Kenyon C Chang J Gensch E Rudner A Tabtiang RA C. elegans mutant that lives twice as long as wild type Nature 366 461 1993 8247153
  23. [27]Friedman DB Johnson TE A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility Genetics 118 75 86 1988 8608934 PMC1203268
  24. [28]Bluher M Kahn BB Kahn CR Extended longevity in mice lacking the insulin receptor in adipose tissue Science 299 572 574 2003 12543978
  25. [29]Taguchi A Wartschow LM White MF Brain IRS2 Signaling Coordinates Life Span and Nutrient Homeostasis Science 317 369 372 2007 17641201
  26. [30]Barzilai N Ferrucci L Insulin Resistance and Aging: A Cause or a Protective Response? J Gerontol A Biol Sci Med Sci 2012 22859390
  27. [31]Mair W Dillin A Aging and survival: the genetics of life span extension by dietary restriction Annu Rev Biochem 77 727 754 2008 18373439
  28. [32]Jiang T Yin F Yao J Brinton RD Cadenas E Lipoic acid restores age-associated impairment of brain energy metabolism through the modulation of Akt/JNK signaling and PGC1a transcriptional pathway Aging Cell 12 1021 1031 2013 23815272 PMC3819405
  29. [33]Liu Z Patil IY Jiang T Sancheti H Walsh JP Stiles BL Yin F Cadenas E High-fat diet induces hepatic insulin resistance and impairment of synaptic plasticity PLoS One 10 e0128274 2015 26023930 PMC4449222
  30. [34]Sancheti H Akopian G Yin F Brinton RD Walsh JP Cadenas E Age-dependent modulation of synaptic plasticity and insulin mimetic effect of lipoic acid on a mouse model of Alzheimer’s disease PLoS One 8 e69830 2013 23875003 PMC3714252
  31. [35]Ho L Qin W Pompl PN Xiang Z Wang J Zhao Z Peng Y Cambareri G Rocher A Mobbs CV Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer’s disease FASEB J 18 902 904 2004 15033922
  32. [37]Cao D Lu H Lewis TL Li L Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease J Biol Chem 282 36275 36282 2007 17942401
  33. [38]Talbot K Wang HY Kazi H Han LY Bakshi KP Stucky A Fuino RL Kawaguchi KR Samoyedny AJ Wilson RS Arvanitakis Z Schneider JA Wolf BA Bennett DA Trojanowski JQ Arnold SE Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline J Clin Invest 122 1316 1338 2012 22476197 PMC3314463
  34. [39]Liu Y Liu F Grundke-Iqbal I Iqbal K Gong C-X Deficient brain insulin signalling pathway in Alzheimer’s disease and diabetes J Pathol 225 54 62 2011 21598254 PMC4484598
  35. [40]Kuusisto J Koivisto K Mykkänen L Helkala EL Vanhanen M Hänninen T Kervinen K Kesäniemi YA Riekkinen PJ Laakso M Association between features of the insulin resistance syndrome and alzheimer’s disease independently of apolipoprotein e4 phenotype: cross sectional population based study BMJ 315 1045 1049 1997 9366728 PMC2127678
  36. [41]Craft S Cholerton B Baker LD Insulin and Alzheimer’s disease: untangling the web J Alzheimers Dis 33 Suppl 1 S263 275 2013 22936011
  37. [43]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 Brain fuel metabolism, aging, and Alzheimer’s disease Nutrition 27 3 20 2011 21035308 PMC3478067
  38. [44]Mergenthaler P Lindauer U Dienel GA Meisel A Sugar for the brain: the role of glucose in physiological and pathological brain function Trends Neurosci 36 587 597 2013 23968694 PMC3900881
  39. [45]Craft S Insulin resistance syndrome and alzheimer disease: pathophysiologic mechanisms and therapeutic implications Alzheimer Dis Assoc Disord 20 298 301 2006 17132977
  40. [46]Gage FH Kelly PA Bjorklund A Regional changes in brain glucose metabolism reflect cognitive impairments in aged rats J Neurosci 4 2856 2865 1984 6502208 PMC6564735
  41. [47]Yin F Yao J Sancheti H Feng T Melcangi RC Morgan TE Finch CE Pike CJ Mack WJ Cadenas E Brinton RD The perimenopausal aging transition in the female rat brain: decline in bioenergetic systems and synaptic plasticity Neurobiol Aging 36 2282 2295 2015 25921624 PMC4416218
  42. [48]Pardo JV Lee JT Sheikh SA Surerus-Johnson C Shah H Munch KR Carlis JV Lewis SM Kuskowski MA Dysken MW Where the brain grows old: Decline in anterior cingulate and medial prefrontal function with normal aging Neuroimage 35 1231 1237 2007 17321756 PMC1913629
  43. [49]Salat DH Buckner RL Snyder AZ Greve DN Desikan RS Busa E Morris JC Dale AM Fischl B Thinning of the Cerebral Cortex in Aging Cereb Cortex 14 721 730 2004 15054051
  44. [50]Sowell ER Peterson BS Thompson PM Welcome SE Henkenius AL Toga AW Mapping cortical change across the human life span Nat Neurosci 6 309 315 2003 12548289
  45. [51]Kochunov P Mangin JF Coyle T Lancaster J Thompson P Riviere D Cointepas Y Régis J Schlosser A Royall DR Age-related morphology trends of cortical sulci Hum Brain Mapp 26 210 220 2005 16161162 PMC6871665
  46. [52]Mosconi L Tsui WH Herholz K Pupi A Drzezga A Lucignani G Reiman EM Holthoff V Kalbe E Sorbi S Diehl-Schmid J Perneczky R Clerici F Caselli R Beuthien-Baumann B Kurz A Minoshima S de Leon MJ Multicenter Standardized 18F-FDG PET Diagnosis of Mild Cognitive Impairment, Alzheimer’s Disease, and Other Dementias J Nucl Med 49 390 398 2008 18287270 PMC3703818
  47. [53]Mosconi L Tsui WH Pupi A De Santi S Drzezga A Minoshima S de Leon MJ 18F-FDG PET Database of Longitudinally Confirmed Healthy Elderly Individuals Improves Detection of Mild Cognitive Impairment and Alzheimer’s Disease J Nucl Med 48 1129 1134 2007 17574982
  48. [54]Alexander GE Chen K Pietrini P Rapoport SI Reiman EM Longitudinal PET Evaluation of Cerebral Metabolic Decline in Dementia: A Potential Outcome Measure in Alzheimer’s Disease Treatment Studies Am J Psychiatry 159 738 745 2002 11986126
  49. [55]Mooradian AD Morin AM Cipp LJ Haspel HC Glucose transport is reduced in the blood-brain barrier of aged rats Brain Res 551 145 149 1991 1913147
  50. [56]Hooijmans CR Graven C Dederen PJ Tanila H van Groen T Kiliaan AJ Amyloid beta deposition is related to decreased glucose transporter-1 levels and hippocampal atrophy in brains of aged APP/PS1 mice Brain Res 1181 93 103 2007 17916337
  51. [57]Ding F Yao J Rettberg JR Chen S Brinton RD Early decline in glucose transport and metabolism precedes shift to ketogenic system in female aging and Alzheimer’s mouse brain: implication for bioenergetic intervention PLoS One 8 e79977 2013 24244584 PMC3823655
  52. [58]Simpson IA Chundu KR Davies-Hill T Honer WG Davies P Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer’s disease Ann Neurol 35 546 551 1994 8179300
  53. [59]Liu Y Liu F Iqbal K Grundke-Iqbal I Gong CX Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease FEBS Lett 582 359 364 2008 18174027 PMC2247364
  54. [60]Harr SD Simonian NA Hyman BT Functional Alterations in Alzheimer’s Disease: Decreased Glucose Transporter 3 Immunoreactivity in the Perforant Pathway Terminal Zone J Neuropathol Exp Neurol 54 38 41 1995 7815078
  55. [61]Kalaria RN Harik SI Reduced glucose transporter at the blood-brain barrier and in cerebral cortex in Alzheimer disease J Neurochem 53 1083 1088 1989 2769254
  56. [63]Magistretti P Allaman I Brain Energy Metabolism Pfaff D Neuroscience in the 21st Century Springer New York 2013 1591 1620
  57. [64]McCommis KS Finck BN Mitochondrial pyruvate transport: A historial perspective and future research directions Biochem J 466 443 454 2015 25748677 PMC4464838
  58. [65]Bender T Martinou J-C The mitochondrial pyruvate carrier in health and disease: To carry or not to carry? Biochim Biophys Acta in press 2016 26826034
  59. [66]Sheu KF Kim YT Blass JP Weksler ME An immunochemical study of the pyruvate dehydrogenase deficit in Alzheimer’s disease brain Ann Neurol 17 444 449 1985 4004169
  60. [67]Nave K-A Werner HB Myelination of the nervous systems: mechanisms and functions Annu Rev Cell Dev Biol 30 503 533 2014 25288117
  61. [68]Birsoy K Wang T Chen WW Frinkman E Abu-remaileh M Sabatini DM An essential role of the mitochondrial electron transport chain in cell proliferation is to enable aspartate synthesis Cell 162 540 551 2015 26232224 PMC4522279
  62. [70]Bak LK Schousboe A Waagepetersen HS The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer J Neurochem 98 641 653 2006 16787421
  63. [71]Boumezbeur F Mason GF de Graaf RA Behar KL Cline GW Shulman GI Rothman DL Petersen KF Altered brain mitochondrial metabolism in healthy aging as assessed by in vivo magnetic resonance spectroscopy J Cereb Blood Flow Metab 30 211 221 2010 19794401 PMC2949111
  64. [72]Rothman DL Behar KL Hyder F Shulman RG In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: implications for brain function Annu Rev Physiol 65 401 427 2003 12524459
  65. [73]Miccheli A Puccetti C Capuani G Di Cocco ME Giardino L Calzà L Battaglia A Battistin L Conti F [1-13C]Glucose entry in neuronal and astrocytic intermediary metabolism of aged rats: A study of the effects of nicergoline treatment by 13C NMR spectroscopy Brain Res 966 116 125 2003 12646315
  66. [74]Nomura Y Yamanaka Y Kitamura Y Arima T Ohnuki T Oomura Y Sasaki K Nagashima K Ihara Y Senescence-accelerated mouse. Neurochemical studies on aging Ann N Y Acad Sci 786 410 418 1996 8687038
  67. [75]Kondziella D Hammer J Sletvold O Sonnewald U The pentylenetetrazole-kindling model of epilepsy in SAMP8 mice: glial–neuronal metabolic interactions Neurochem Int 43 629 637 2003 12892650
  68. [76]Hyder F Patel AB Gjedde A Rothman DL Behar KL Shulman RG Neuronal–Glial Glucose Oxidation and Glutamatergic–GABAergic Function J Cereb Blood Flow Metab 26 865 877 2006 16407855
  69. [77]Dedeoglu A Choi J-K Cormier K Kowall NW Jenkins BG Magnetic resonance spectroscopic analysis of Alzheimer’s disease mouse brain that express mutant human APP shows altered neurochemical profile Brain Res 1012 60 65 2004 15158161
  70. [78]Tiwari V Patel AB Impaired glutamatergic and GABAergic function at early age in AβPPswe-PS1dE9 mice: implications for Alzheimer’s disease J Alzheimers Dis 28 765 769 2012 22112551
  71. [79]Doert A Pilatus U Zanella F Müller WE Eckert GP 1H-and 13C-NMR spectroscopy of Thy-1-APPSL mice brain extracts indicates metabolic changes in Alzheimer’s disease J Neural Transm (Vienna) 122 541 550 2015 25742870
  72. [80]Sancheti H Kanamori K Patil I Brinton RD Ross BD Cadenas E Reversal of metabolic deficits by lipoic acid in a triple transgenic mouse model of Alzheimer’s disease: A 13C NMR study J Cereb Blood Flow Metab 34 288 296 2014 24220168 PMC3915206
  73. [81]Lin AP Shic F Enriquez C Ross BD Reduced glutamate neurotransmission in patients with Alzheimer’s disease–an in vivo 13C magnetic resonance spectroscopy study MAGMA 16 29 42 2003 12695884
  74. [82]Sancheti H Patil I Kanamori K Diaz Brinton R Zhang W Lin AL Cadenas E Hypermetabolic state in the 7-month-old triple transgenic mouse model of Alzheimer’s disease and the effect of lipoic acid: a (13)C-NMR study J Cereb Blood Flow Metab 34 1749 1760 2014 25099753 PMC4269751
  75. [84]Drew B Leeuwenburgh C Ageing and subcellular distribution of mitochondria: role of mitochondrial DNA deletions and energy production Acta Physiol Scand 182 333 341 2004 15569094
  76. [85]Navarro A Boveris A Mitochondrial nitric oxide synthase, mitochondrial brain dysfunction in aging, and mitochondria-targeted antioxidants Adv Drug Deliv Rev 60 1534 1544 2008 18647625
  77. [86]Bowling AC Mutisya EM Walker LC Price DL Cork LC Beal MF Age-Dependent Impairment of Mitochondrial Function in Primate Brain J Neurochem 60 1964 1967 1993 8473911
  78. [87]Petrosillo G Matera M Casanova G Ruggiero FM Paradies G Mitochondrial dysfunction in rat brain with aging: Involvement of complex I, reactive oxygen species and cardiolipin Neurochem Int 53 126 131 2008 18657582
  79. [88]Hauptmann S Scherping I Drose S Brandt U Schulz KL Jendrach M Leuner K Eckert A Muller WE Mitochondrial dysfunction: an early event in Alzheimer pathology accumulates with age in AD transgenic mice Neurobiol Aging 30 1574 1586 2009 18295378
  80. [89]Yao J Irwin RW Zhao L Nilsen J Hamilton RT Brinton RD Mitochondrial bioenergetic deficit precedes Alzheimer’s pathology in female mouse model of Alzheimer’s disease Proc Natl Acad Sci USA 106 14670 14675 2009 19667196 PMC2732886
  81. [90]Fukuyama R Hatanpää K Rapoport SI Chandrasekaran K Gene expression of ND4, a subunit of complex I of oxidative phosphorylation in mitochondria, is decreased in temporal cortex of brains of Alzheimer’s disease patients Brain Res 713 290 293 1996 8725003
  82. [91]Kim SH Vlkolinsky R Cairns N Lubec G Decreased levels of complex III core protein 1 and complex V β chain in brains from patients with Alzheimer’s disease and Down syndrome Cell Mol Life Sci 57 1810 1816 2000 11130185 PMC11146938
  83. [92]Parker WDJ Parks J Filley CM Kleinschmidt-DeMasters BK Electron transport chain defects in Alzheimer’s disease brain Neurology 44 1090 1994 8208407
  84. [93]Kish SJ Bergeron C Rajput A Dozic S Mastrogiacomo F Chang LJ Wilson JM DiStefano LM Nobrega JN Brain Cytochrome Oxidase in Alzheimer’s Disease J Neurochem 59 776 779 1992 1321237
  85. [94]Dragicevic N Mamcarz M Zhu Y Buzzeo R Tan J Arendash GW Bradshaw PC Mitochondrial amyloid-beta levels are associated with the extent of mitochondrial dysfunction in different brain regions and the degree of cognitive impairment in Alzheimer’s transgenic mice J Alzheimers Dis 20 Suppl 2 S535 550 2010 20463404
  86. [95]Bobba A Amadoro G Valenti D Corsetti V Lassandro R Atlante A Mitochondrial respiratory chain Complexes I and IV are impaired by beta-amyloid via direct interaction and through Complex I-dependent ROS production, respectively Mitochondrion 13 298 311 2013 23562762
  87. [96]Markesbery W Oxidative Stress Hypothesis in Alzheimer’s Disease Free Radic Biol Med 23 134 147 1997 9165306
  88. [98]Boveris A Cadenas E Mitochondrial production of superoxide anions and its relationship to the antimycin-insensitive respiration FEBS Lett 54 311 314 1975 236930
  89. [99]Boveris A Cadenas E Stoppani AOM Role of ubiquinone in the mitochondrial generation of hydrogen peroxide Biochem J 156 435 444 1976 182149 PMC1163765
  90. [100]Cadenas E Boveris A Ragan CI Stoppani AO Production of superoxide radicals and hydrogen peroxide by NADH- ubiquinone reductase and ubiquinol-cytochrome c reductase from beef- heart mitochondria Arch Biochem Biophys 180 248 257 1977 195520
  91. [102]Rhee SG Cell signaling: H2O2, a necessary evil for cell signaling Science 312 1882 1883 2006 16809515
  92. [103]Storozhevykh TP Senilova YE Persiyantseva NA Pinelis VG Pomytkin IA Mitochondrial respiratory chain is involved in insulin-stimulated hydrogen peroxide production and plays an integral role in insulin receptor autophosphorylation in neurons BMC NeuroSci 8 84 2007 17919343 PMC2089077
  93. [104]Persiyantseva NA Storozhevykh TP Senilova YE Gorbacheva LR Pinelis VG Pomytkin IA Mitochondrial H2O2 as an enable signal for triggering autophosphorylation of insulin receptor in neurons J Mol Signal 8 11 2013 24094269 PMC3817577
  94. [105]Loh K Deng H Fukushima A Cai X Boivin B Galic S Bruce C Shields BJ Skiba B Ooms LM Stepto N Wu B Mitchell CA Tonks NK Watt MJ Febbraio MA Crack PJ Andrikopoulos S Tiganis T Reactive oxygen species enhance insulin sensitivity Cell Metab 10 260 272 2009 19808019 PMC2892288
  95. [106]Elchebly M Payette P Michaliszyn E Cromlish W Collins S Loy AL Normandin D Cheng A Himms-Hagen J Chan CC Ramachandran C Gresser MJ Tremblay ML Kennedy BP Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene Science 283 1544 1548 1999 10066179
  96. [107]Antico Arciuch VG Galli S Franco MC Lam PY Cadenas E Carreras MC Poderoso JJ Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression PLoS One 4 e7523 2009 19844585 PMC2761088
  97. [108]Iwakami S Misu H Takeda T Sugimori M Matsugo S Kaneko S Takamura T Concentration-dependent dual effects of hydrogen peroxide on insulin signal transduction in H4IIEC hepatocytes PLoS One 6 e27401 2011 22102892 PMC3216925
  98. [109]Aguirre V Uchida T Yenush L Davis R White MF The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307) J Biol Chem 275 9047 9054 2000 10722755
  99. [110]Zhou Q Lam PY Han D Cadenas E c-Jun N-terminal kinase regulates mitochondrial bioenergetics by modulating pyruvate dehydrogenase activity in primary cortical neurons J Neurochem 104 325 335 2008 17949412
  100. [112]Yin F Sancheti H Cadenas E Silencing of nicotinamide nucleotide transhydrogenase impairs cellular redox homeostasis and energy metabolism in PC12 cells Biochim Biophys Acta 1817 401 409 2012 22198343 PMC3269566
  101. [113]Pinzar E Wang T Garrido MR Xu W Levy P Bottari SP Angiotensin II induces tyrosine nitration and activation of ERK1/2 in vascular smooth muscle cells FEBS Lett 579 5100 5104 2005 16139272
  102. [114]Saitoh M Nishitoh H Fujii M Takeda K Tobiume K Sawada Y Kawabata M Miyazono K Ichijo H Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1 EMBO J 17 2596 2606 1998 9564042 PMC1170601
  103. [115]Foley TD Armstrong JJ Kupchak BR Identification and H2O2 sensitivity of the major constitutive MAPK phosphatase from rat brain Biochem Biophys Res Commun 315 568 574 2004 14975738
  104. [116]Adler V Funchs SY Benezra M Rosario L Tew KD Pincus MR Sardana M Henderson CJ Wolf CR Davis RJ Ronai Z Regulation of JNK signaling by GSTp EMBO J 18 1321 1234 1999 10064598 PMC1171222
  105. [118]Tramutola A Triplett JC Di Domenico F Niedowicz DM Murphy MP Coccia R Perluigi M Butterfield DA Alteration of mTOR signaling occurs early in the progression of Alzheimer disease (AD): analysis of brain from subjects with pre-clinical AD, amnestic mild cognitive impairment and late-stage AD J Neurochem 133 739 749 2015 25645581
  106. [119]Rhee SG Woo HA Multiple functions of peroxiredoxins: peroxidases, sensors and regulators of the intracellular messenger HO, and protein chaperones Antioxid Redox Signal 15 781 794 2011 20919930
  107. [120]Dabkowski ER Williamson CL Hollander JM Mitochondria-specific transgenic overexpression of phospholipid hydroperoxide glutathione peroxidase (GPx4) attenuates ischemia/reperfusion-associated cardiac dysfunction Free Radic Biol Med 45 855 865 2008 18638546
  108. [121]Yoo MH Gu X Xu XM Kim JY Carlson BA Patterson AD Cai H Gladyshev VN Hatfield DL Delineating the role of glutathione peroxidase 4 in protecting cells against lipid hydroperoxide damage and in Alzheimer’s disease Antioxid Redox Signal 12 819 827 2010 19769463 PMC2861544
  109. [122]Shan X Jones DP Hashmi M Anders MW Selective depletion of mitochondrial glutathione concentrations by (R,S)-3-hydroxy-4-pentenoate potentiates oxidative cell death Chem Res Toxicol 6 75 81 1993 8448354
  110. [123]Muyderman H Nilsson M Sims NR Highly selective and prolonged depletion of mitochondrial glutathione in astrocytes markedly increases sensitivity to peroxynitrite J Neurosci 24 8019 8028 2004 15371502 PMC6729783
  111. [124]Wüllner U Seyfried J Groscurth P Beinroth S Winter S Gleichmann M Heneka M Löschmann PA Schulz JB Weller M Klockgether T Glutathione depletion and neuronal cell death: the role of reactive oxygen intermediates and mitochondrial function Brain Res 826 53 62 1999 10216196
  112. [125]Muyderman H Wadey AL Nilsson M Sims NR Mitochondrial glutathione protects against cell death induced by oxidative and nitrative stress in astrocytes J Neurochem 102 1369 1382 2007 17484727
  113. [126]Jia Z Zhu H Misra HP Li Y Potent induction of total cellular GSH and NQO1 as well as mitochondrial GSH by 3H-1,2-dithiole-3-thione in SH-SY5Y neuroblastoma cells and primary human neurons: Protection against neurocytotoxicity elicited by dopamine, 6-hydroxydopamine, 4-hydroxy-2-nonenal, or hydrogen peroxide Brain Res 1197 159 169 2008 18234165 PMC2386954
  114. [127]Giustarini D Dalle-Donne I Milzani A Rossi R Low molecular mass thiols, disulfides and protein mixed disulfides in rat tissues: influence of sample manipulation, oxidative stress and ageing Mech Ageing Dev 132 141 148 2011 21335026
  115. [128]Rebrin I Kamzalov S Sohal RS Effects of age and caloric restriction on glutathione redox state in mice Free Radic Biol Med 35 626 635 2003 12957655 PMC2837076
  116. [129]Vina J Sastre J Anton V Bruseghini L Esteras A Asensi M Effect of aging on glutathione metabolism. Protection by antioxidants EXS 62 136 144 1992 1450581
  117. [130]Asuncion J Millan A Pla R Bruseghini L Esteras A Pallardo F Sastre J Vina J Mitochondrial glutathione oxidation correlates with age-associated oxidative damage to mitochondrial DNA FASEB J 10 333 338 1996 8641567
  118. [131]Emir UE Raatz S McPherson S Hodges JS Torkelson C Tawfik P White T Terpstra M Noninvasive quantification of ascorbate and glutathione concentration in the elderly human brain NMR Biomed 24 888 894 2011 21834011 PMC3118919
  119. [132]Cruz-Aguado R Almaguer-Melian W Diaz CM Lorigados L Bergado J Behavioral and biochemical effects of glutathione depletion in the rat brain Brain Res Bull 55 327 333 2001 11489339
  120. [133]Dean O Bush AI Berk M Copolov DL van den Buuse M Glutathione depletion in the brain disrupts short-term spatial memory in the Y-maze in rats and mice Behav Brain Res 198 258 262 2009 19061918
  121. [134]Zhang H Go YM Jones DP Mitochondrial thioredoxin-2/peroxiredoxin-3 system functions in parallel with mitochondrial GSH system in protection against oxidative stress Arch Biochem Biophys 465 119 126 2007 17548047
  122. [135]Peng Y Yang PH Guo Y Ng SS Liu J Fung PC Tay D Ge J He ML Kung HF Lin MC Catalase and peroxiredoxin 5 protect Xenopus embryos against alcohol-induced ocular anomalies Invest Ophth Vis Sci 45 23 29 2004 14691149
  123. [136]Cox AG Peskin AV Paton LN Winterbourn CC Hampton MB Redox potential and peroxide reactivity of human peroxiredoxin 3 Biochemistry 48 6495 6501 2009 19462976
  124. [138]Cox AG Pearson AG Pullar JM Jonsson TJ Lowther WT Winterbourn CC Hampton MB Mitochondrial peroxiredoxin 3 is more resilient to hyperoxidation than cytoplasmic peroxiredoxins Biochem J 421 51 58 2009 19356151 PMC3745641
  125. [139]Rhee SG Jeong W Chang TS Woo HA Sulfiredoxin, the cysteine sulfinic acid reductase specific to 2-Cys peroxiredoxin: its discovery, mechanism of action, and biological significance Kidney Int Suppl S3 8 2007 17653208
  126. [140]Noh YH Baek JY Jeong W Rhee SG Chang TS Sulfiredoxin Translocation into Mitochondria Plays a Crucial Role in Reducing Hyperoxidized Peroxiredoxin III J Biol Chem 284 8470 8477 2009 19176523 PMC2659205
  127. [141]Musicco C Capelli V Pesce V Timperio AM Calvani M Mosconi L Zolla L Cantatore P Gadaleta MN Accumulation of overoxidized Peroxiredoxin III in aged rat liver mitochondria Biochim Biophys Acta 1787 890 896 2009 19272351
  128. [142]Ngo JK Davies KJ Importance of the lon protease in mitochondrial maintenance and the significance of declining lon in aging Ann N Y Acad Sci 1119 78 87 2007 18056957
  129. [143]Hattori F Murayama N Noshita T Oikawa S Mitochondrial peroxiredoxin-3 protects hippocampal neurons from excitotoxic injury in vivo J Neurochem 86 860 868 2003 12887684
  130. [144]Krapfenbauer K Engidawork E Cairns N Fountoulakis M Lubec G Aberrant expression of peroxiredoxin subtypes in neurodegenerative disorders Brain Res 967 152 160 2003 12650976
  131. [145]Kim SH Fountoulakis M Cairns N Lubec G Protein levels of human peroxiredoxin subtypes in brains of patients with Alzheimer’s disease and Down syndrome J Neural Transm Suppl 223 235 2001 11771746
  132. [146]Chen L Na R Ran Q Enhanced defense against mitochondrial hydrogen peroxide attenuates age-associated cognition decline Neurobiol Aging 35 2552 2561 2014 24906890
  133. [147]Seo MS Kang SW Kim K Baines IC Lee TH Rhee SG Identification of a new type of mammalian peroxiredoxin that forms an intramolecular disulfide as a reaction intermediate J Biol Chem 275 20346 20354 2000 10751410
  134. [148]Trujillo M Clippe A Manta B Ferrer-Sueta G Smeets A Declercq JP Knoops B Radi R Pre-steady state kinetic characterization of human peroxiredoxin 5: taking advantage of Trp84 fluorescence increase upon oxidation Arch Biochem Biophys 467 95 106 2007 17892856
  135. [149]De Simoni S Goemaere J Knoops B Silencing of peroxiredoxin 3 and peroxiredoxin 5 reveals the role of mitochondrial peroxiredoxins in the protection of human neuroblastoma SH-SY5Y cells toward MPP+ Neurosci Lett 433 219 224 2008 18262354
  136. [150]Radyuk SN Michalak K Klichko VI Benes J Rebrin I Sohal RS Orr WC Peroxiredoxin 5 confers protection against oxidative stress and apoptosis and also promotes longevity in Drosophila Biochem J 419 437 445 2009 19128239 PMC2842572
  137. [151]Banmeyer I Marchand C Clippe A Knoops B Human mitochondrial peroxiredoxin 5 protects from mitochondrial DNA damages induced by hydrogen peroxide FEBS Lett 579 2327 2333 2005 15848167
  138. [152]Jarvis RM Hughes SM Ledgerwood EC Peroxiredoxin 1 functions as a signal peroxidase to receive, transduce, and transmit peroxide signals in mammalian cells Free Radic Biol Med 53 1522 1530 2012 22902630
  139. [153]Sobotta MC Liou W Stocker S Talwar D Oehler M Ruppert T Scharf AN Dick TP Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling Nat Chem Biol 11 64 70 2015 25402766
  140. [154]Miranda-Vizuete A Damdimopoulos AE Spyrou G The mitochondrial thioredoxin system Antioxid Redox Signal 2 801 810 2000 11213484
  141. [155]Spyrou G Enmark E Miranda-Vizuete A Gustafsson J Cloning and expression of a novel mammalian thioredoxin J Biol Chem 272 2936 2941 1997 9006939
  142. [156]Zhang R Al-Lamki R Bai L Streb JW Miano JM Bradley J Min W Thioredoxin-2 inhibits mitochondria-located ASK1-mediated apoptosis in a JNK-independent manner Circ Res 94 1483 1491 2004 15117824
  143. [157]Rojanathammanee L Rakoczy S Brown-Borg HM Growth hormone alters the glutathione S-transferase and mitochondrial thioredoxin systems in long-living Ames dwarf mice J Gerontol A Biol Sci Med Sci 69 1199 1211 2014 24285747 PMC4172038
  144. [158]Arodin L Lamparter H Karlsson H Nennesmo I Bjornstedt M Schroder J Fernandes AP Alteration of thioredoxin and glutaredoxin in the progression of Alzheimer’s disease J Alzheimers Dis 39 787 797 2014 24270206
  145. [159]Rohrbach S Gruenler S Teschner M Holtz J The thioredoxin system in aging muscle: key role of mitochondrial thioredoxin reductase in the protective effects of caloric restriction? Am J Physiol Regul Integr Comp Physiol 291 R927 R935 2006 16675629
  146. [160]Patenaude A Ven Murthy MR Mirault ME Mitochondrial thioredoxin system: effects of TrxR2 overexpression on redox balance, cell growth, and apoptosis J Biol Chem 279 27302 27314 2004 15082714
  147. [162]Hoek JB Rydström J Physiological roles of nicotinamide nucleotide transhydrogenase Biochem J 254 1 10 1988 3052428 PMC1135030
  148. [163]Agarwal AR Zhao L Sancheti H Sundar IK Rahman I Cadenas E Short-term cigarette smoke exposure induces reversible changes in energy metabolism and cellular redox status independent of inflammatory responses in mouse lungs Am J Physiol-Lung C 303 L889 898 2012 23064950
  149. [164]Lopert P Patel M Nicotinamide nucleotide transhydrogenase (Nnt) links the substrate requirement in brain mitochondria for hydrogen peroxide removal to the thioredoxin/peroxiredoxin (Trx/Prx) system J Biol Chem 289 15611 15620 2014 24722990 PMC4140916
  150. [165]Ghosh D Levault KR Brewer GJ Relative importance of redox buffers GSH and NAD(P)H in age-related neurodegeneration and Alzheimer disease-like mouse neurons Aging Cell 13 631 640 2014 24655393 PMC4116450
  151. [166]Nickel AG von Hardenberg A Hohl M Loffler JR Kohlhaas M Becker J Reil JC Kazakov A Bonnekoh J Stadelmaier M Puhl SL Wagner M Bogeski I Cortassa S Kappl R Pasieka B Lafontaine M Lancaster CR Blacker TS Hall AR Duchen MR Kastner L Lipp P Zeller T Muller C Knopp A Laufs U Bohm M Hoth M Maack C Reversal of Mitochondrial Transhydrogenase Causes Oxidative Stress in Heart Failure Cell Metab 22 472 484 2015 26256392
  152. [168]Nulton-Persson AC Starke DW Mieyal JJ Szweda LI Reversible inactivation of alpha-ketoglutarate dehydrogenase in response to alterations in the mitochondrial glutathione status Biochemistry 42 4235 4242 2003 12680778
  153. [170]Garcia J Han D Sancheti H Yap LP Kaplowitz N Cadenas E Regulation of mitochondrial glutathione redox status and protein glutathionylation by respiratory substrates J Biol Chem 285 39646 39654 2010 20937819 PMC3000945
  154. [171]Lam PY Yin F Hamilton RT Boveris A Cadenas E Elevated neuronal nitric oxide synthase expression during ageing and mitochondrial energy production Free Radic Res 43 431 439 2009 19347761 PMC3319075
  155. [172]Taylor ER Hurrell F Shannon RJ Lin TK Hirst J Murphy MP Reversible glutathionylation of complex I increases mitochondrial superoxide formation J Biol Chem 278 19603 19610 2003 12649289
  156. [173]Chen YR Chen CL Pfeiffer DR Zweier JL Mitochondrial complex II in the post-ischemic heart: oxidative injury and the role of protein S-glutathionylation J Biol Chem 282 32640 32654 2007 17848555
  157. [174]Bubber P Haroutunian V Fisch G Blass JP Gibson GE Mitochondrial abnormalities in Alzheimer brain: mechanistic implications Ann Neurol 57 695 703 2005 15852400
  158. [175]Sultana R Butterfield DA Oxidatively modified, mitochondria-relevant brain proteins in subjects with Alzheimer disease and mild cognitive impairment J Bioenerg Biomembr 41 441 446 2009 19777328 PMC2920455
  159. [176]Agarwal AR Yin F Cadenas E Short-term cigarette smoke exposure leads to metabolic alterations in lung alveolar cells Am J Respir Cell Mol 51 284 293 2014 24625219
  160. [177]Agarwal AR Yin F Cadenas E Metabolic shift in lung alveolar cell mitochondria following acrolein exposure Am J Physiol Lung Cell Mol Physiol 305 L764 773 2013 24056970
  161. [178]Carson MJ Doose JM Melchior B Schmid CD Ploix CC CNS immune privilege: hiding in plain sight Immunol Rev 213 48 65 2006 16972896 PMC2633103
  162. [179]Farina C Aloisi F Meinl E Astrocytes are active players in cerebral innate immunity Trends Immunol 28 138 145 2007 17276138
  163. [181]Janssen-Heininger YM Poynter ME Baeuerle PA Recent advances towards understanding redox mechanisms in the activation of nuclear factor kappaB Free Radic Biol Med 28 1317 1327 2000 10924851
  164. [182]Kabe Y Ando K Hirao S Yoshida M Handa H Redox regulation of NF-kappaB activation: distinct redox regulation between the cytoplasm and the nucleus Antioxid Redox Signal 7 395 403 2005 15706086
  165. [183]Weinberg SE Sena LA Chandel NS Mitochondria in the Regulation of Innate and Adaptive Immunity Immunity 42 406 417 2015 25786173 PMC4365295
  166. [184]Patten DA Germain M Kelly MA Slack RS Reactive oxygen species: stuck in the middle of neurodegeneration J Alzheimers Dis 20 Suppl 2 S357 367 2010 20421690
  167. [185]Takada Y Mukhopadhyay A Kundu GC Mahabeleshwar GH Singh S Aggarwal BB Hydrogen peroxide activates NF-kappa B through tyrosine phosphorylation of I kappa B alpha and serine phosphorylation of p65: evidence for the involvement of I kappa B alpha kinase and Syk protein-tyrosine kinase J Biol Chem 278 24233 24241 2003 12711606
  168. [186]Pahl HL Activators and target genes of Rel/NF-kappaB transcription factors Oncogene 18 6853 6866 1999 10602461
  169. [187]Das KC Lewis-Molock Y White CW Activation of NF-kappa B and elevation of MnSOD gene expression by thiol reducing agents in lung adenocarcinoma (A549) cells Am J Physiol 269 L588 602 1995 7491977
  170. [188]Bubici C Papa S Dean K Franzoso G Mutual cross-talk between reactive oxygen species and nuclear factor-kappa B: molecular basis and biological significance Oncogene 25 6731 6748 2006 17072325
  171. [189]Song YS Park HJ Kim SY Lee SH Yoo HS Lee HS Lee MK Oh KW Kang SK Lee SE Hong JT Protective role of Bcl-2 on beta-amyloid-induced cell death of differentiated PC12 cells: reduction of NF-kappaB and p38 MAP kinase activation Neurosci Res 49 69 80 2004 15099705
  172. [190]Chongthammakun V Sanvarinda Y Chongthammakun S Reactive oxygen species production and MAPK activation are implicated in tetrahydrobiopterin-induced SH-SY5Y cell death Neurosci Lett 449 178 182 2009 19013215
  173. [191]Chen L Liu L Yin J Luo Y Huang S Hydrogen peroxide-induced neuronal apoptosis is associated with inhibition of protein phosphatase 2A and 5, leading to activation of MAPK pathway Int J Biochem Cell Biol 41 1284 1295 2009 19038359
  174. [192]Patel JR Brewer GJ Age-related differences in NFkappaB translocation and Bcl-2/Bax ratio caused by TNFalpha and Abeta42 promote survival in middle-age neurons and death in old neurons Exp Neurol 213 93 100 2008 18625500 PMC2597588
  175. [195]Abais JM Xia M Zhang Y Boini KM Li PL Redox regulation of NLRP3 inflammasomes: ROS as trigger or effector? Antioxid Redox Signal 22 1111 1129 2015 25330206 PMC4403231
  176. [196]Rathinam VA Vanaja SK Fitzgerald KA Regulation of inflammasome signaling Nature immunology 13 333 342 2012 22430786 PMC3523703
  177. [197]Minkiewicz J de Rivero Vaccari JP Keane RW Human astrocytes express a novel NLRP2 inflammasome Glia 61 1113 1121 2013 23625868
  178. [198]Kahlenberg JM Dubyak GR Mechanisms of caspase-1 activation by P2X7 receptor-mediated K+ release Am J Physiol Cell Physiol 286 C1100 1108 2004 15075209
  179. [199]Kanneganti TD Lamkanfi M Kim YG Chen G Park JH Franchi L Vandenabeele P Nunez G Pannexin-1-mediated recognition of bacterial molecules activates the cryopyrin inflammasome independent of Toll-like receptor signaling Immunity 26 433 443 2007 17433728
  180. [204]Tschopp J Schroder K NLRP3 inflammasome activation: The convergence of multiple signalling pathways on ROS production? Nature reviews. Immunology 10 210 215 2010 20168318
  181. [205]Spindel ON Berk BC Redox redux: protecting the ischemic myocardium J Clin Invest 122 30 32 2012 22201673 PMC3248805
  182. [207]Meissner F Molawi K Zychlinsky A Superoxide dismutase 1 regulates caspase-1 and endotoxic shock Nat Immunol 9 866 872 2008 18604212
  183. [208]Cruz CM Rinna A Forman HJ Ventura AL Persechini PM Ojcius DM ATP activates a reactive oxygen species-dependent oxidative stress response and secretion of proinflammatory cytokines in macrophages J Biol Chem 282 2871 2879 2007 17132626 PMC2693903
  184. [210]Infanger DW Sharma RV Davisson RL NADPH oxidases of the brain: distribution, regulation, and function Antioxid Redox Signal 8 1583 1596 2006 16987013
  185. [212]Bruce-Keller AJ White CL Gupta S Knight AG Pistell PJ Ingram DK Morrison CD Keller JN NOX activity in brain aging: exacerbation by high fat diet Free Radic Biol Med 49 22 30 2010 20347034 PMC2875353
  186. [213]Zawada WM Banninger GP Thornton J Marriott B Cantu D Rachubinski AL Das M Griffin WS Jones SM Generation of reactive oxygen species in 1-methyl-4-phenylpyridinium (MPP+) treated dopaminergic neurons occurs as an NADPH oxidase-dependent two-wave cascade J Neuroinflammation 8 129 2011 21975039 PMC3198931
  187. [215]Sultana R Poon HF Cai J Pierce WM Merchant M Klein JB Markesbery WR Butterfield DA Identification of nitrated proteins in Alzheimer’s disease brain using a redox proteomics approach Neurobiol Dis 22 76 87 2006 16378731
  188. [216]Hewinson J Moore SF Glover C Watts AG MacKenzie AB A key role for redox signaling in rapid P2X7 receptor-induced IL-1 beta processing in human monocytes J Immunol 180 8410 8420 2008 18523309
  189. [217]Abais JM Xia M Li G Gehr TW Boini KM Li PL Contribution of endogenously produced reactive oxygen species to the activation of podocyte NLRP3 inflammasomes in hyperhomocysteinemia Free Radic Biol Med 67 211 220 2014 24140862 PMC3945111
  190. [218]Haneklaus M O’Neill LA NLRP3 at the interface of metabolism and inflammation Immunol Rev 265 53 62 2015 25879283
  191. [219]Vandanmagsar B Youm YH Ravussin A Galgani JE Stadler K Mynatt RL Ravussin E Stephens JM Dixit VD The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance Nature medicine 17 179 188 2011 PMC3076025 21217695
  192. [220]Wen H Gris D Lei Y Jha S Zhang L Huang MT Brickey WJ Ting JP Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling Nat Immunol 12 408 415 2011 21478880 PMC4090391
  193. [221]Stienstra R Joosten LA Koenen T van Tits B van Diepen JA van den Berg SA Rensen PC Voshol PJ Fantuzzi G Hijmans A Kersten S Muller M van den Berg WB van Rooijen N Wabitsch M Kullberg BJ van der Meer JW Kanneganti T Tack CJ Netea MG The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity Cell metabolism 12 593 605 2010 21109192 PMC3683568
  194. [223]Ehses JA Lacraz G Giroix MH Schmidlin F Coulaud J Kassis N Irminger JC Kergoat M Portha B Homo-Delarche F Donath MY IL-1 antagonism reduces hyperglycemia and tissue inflammation in the type 2 diabetic GK rat Proc Natl Acad Sci USA 106 13998 14003 2009 19666548 PMC2729009
  195. [224]Jager J Gremeaux T Cormont M Le Marchand-Brustel Y Tanti JF Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression Endocrinology 148 241 251 2007 17038556 PMC1971114
  196. [225]Hotamisligil GS Peraldi P Budavari A Ellis R White MF Spiegelman BM IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance Science 271 665 668 1996 8571133
  197. [226]Wilkins HM Carl SM Weber SG Ramanujan SA Festoff BW Linseman DA Swerdlow RH Mitochondrial lysates induce inflammation and Alzheimer’s disease-relevant changes in microglial and neuronal cells J Alzheimers Dis 45 305 318 2015 25537010 PMC4605548
  198. [227]Shimada K Crother TR Karlin J Dagvadorj J Chiba N Chen S Ramanujan VK Wolf AJ Vergnes L Ojcius DM Rentsendorj A Vargas M Guerrero C Wang Y Fitzgerald KA Underhill DM Town T Arditi M Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis Immunity 36 401 414 2012 22342844 PMC3312986
  199. [228]Inoue K Microglial activation by purines and pyrimidines Glia 40 156 163 2002 12379903
  200. [230]Norden DM Godbout JP Review: microglia of the aged brain: primed to be activated and resistant to regulation Neuropathology and applied neurobiology 39 19 34 2013 23039106 PMC3553257

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Authors
Yin, F., Sancheti, H., Patil, I., & Cadenas, E.
Affiliations
University of Southern California (US)
Corresponding author
Yin, Fei
ORCID
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2016-11
Volume
100
Pages
108-122
ISSN
0891-5849 (ISSN-L)
DOI
10.1016/j.freeradbiomed.2016.04.200
PMC
PMC5094909
OpenAlex
W2345747767
Cited by
538
References
31
Citations by year
2026: 55 · 2025: 70 · 2024: 62 · 2023: 66 · 2022: 65 · 2021: 64 · 2020: 64 · 2019: 43 · 2018: 25 · 2017: 16 · 2016: 8
FWCI
3.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
NIH (RO1AG016718)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
brain aging, Alzheimer's disease, brain energy metabolism, mitochondrial dysfunction, oxidative stress, redox regulation, neuroinflammation, microglial activation, inflammatory cytokines, neurodegeneration, glucose availability, hydrogen peroxide
MeSH terms
Aging, Alzheimer Disease, Animals, Brain, Energy Metabolism, Humans, Hydrogen Peroxide, Inflammation, Mitochondria, Oxidation-Reduction, Signal Transduction

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