The energy-redox axis in aging and age-related neurodegeneration

Advanced Drug Delivery Reviews

Volumn 61, Issue 14, 2009, Pages 1283-1298

  Yap, Li Peng ^a   Garcia, Jerome V ^a,c   Han, Derick ^b   Cadenas, Enrique ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^c Department of Psychology   (United States)

Author keywords

Aging; Alzheimer's disease; Energy redox axis; Lipoic acid; Mitochondria; Thiol disulfide exchange

Indexed keywords

AGE-RELATED; AGING PROCESS; ALZHEIMER'S DISEASE; ENERGY METABOLISM; LIPOIC ACIDS; MITOCHONDRIAL ENERGY; MITOCHONDRIAL FUNCTION; MITOCHONDRIAL OXIDANTS; NAD(P)H; NEURODEGENERATION; NEURODEGENERATIVE DISORDERS; POST-TRANSLATIONAL MODIFICATIONS; PROTEIN OXIDATION; REDOX STATUS; TRANSDUCING;

METABOLISM; MITOCHONDRIA; PROTEINS;

ACIDS;

AC 1202; ACETYLCYSTEINE; GLUTATHIONE; INSULIN RECEPTOR; KETONE BODY; LACTIC ACID; NEUROPROTECTIVE AGENT; NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) TRANSHYDROGENASE; NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; OXIDIZING AGENT; PYRUVIC ACID; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; THIOCTIC ACID; THIOREDOXIN; UNCLASSIFIED DRUG;

AGED; AGING; ALZHEIMER DISEASE; ANTIOXIDANT ACTIVITY; BLOOD BRAIN BARRIER; BRAIN INJURY; BRAIN ISCHEMIA; CITRIC ACID CYCLE; CLINICAL EFFECTIVENESS; CLINICAL TRIAL; DEGENERATIVE DISEASE; DIET SUPPLEMENTATION; DRUG MECHANISM; DRUG PENETRATION; DRUG RECEPTOR BINDING; ENERGY METABOLISM; HUMAN; MEMORY DISORDER; MITOCHONDRIAL ENERGY TRANSFER; MITOCHONDRIAL RESPIRATION; NERVE CELL CULTURE; NERVE CELL LESION; NERVE DEGENERATION; NEUROMODULATION; NEUROPROTECTION; NONHUMAN; OXIDATION REDUCTION STATE; OXIDATIVE PHOSPHORYLATION; OXIDATIVE STRESS; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN PROCESSING; REPERFUSION INJURY; REVIEW;

AGING; DRUG DELIVERY SYSTEMS; ENERGY METABOLISM; HUMANS; MITOCHONDRIA; MODELS, BIOLOGICAL; NEURODEGENERATIVE DISEASES; NEURONS; OXIDATION-REDUCTION;

EID: 71549131281     PISSN: 0169409X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.addr.2009.07.015     Document Type: Review

References (170)

1. Watson G.S., and Craft S. The role of insulin resistance in the pathogenesis of Alzheimer's disease: implications for treatment. CNS Drugs 17 (2003) 27-45
2. Yankner B.A., Lu T., and Loerch P. The aging brain. Annual Review of Pathology 3 (2008) 41-66
3. Lam P.Y., Yin F., Hamilton R.T., Boveris A., and Cadenas E. Elevated neuronal nitric oxide synthase expression during ageing and mitochondrial energy production. Free Radical Research 43 (2009) 431-439
4. Tseng B.P., Green K.N., Chan J.L., Blurton-Jones M., and LaFerla F.M. Abeta inhibits the proteasome and enhances amyloid and tau accumulation. Neurobiology of Aging 29 (2008) 1607-1618
5. Mattson M.P., and Magnus T. Ageing and neuronal vulnerability. Nature Review. Neuroscience 7 (2006) 278-294
6. Silverman D.H.S., Small G.W., Chang C.Y., Lu C.S., de Aburto M.A.K., Chen W., Czernin J., Rapoport S.I., Pietrini P., Alexander G.E., Schapiro M.B., Jagust W.J., Hoffman J.M., Welsh-Bohmer K.A., Alavi A., Clark C.M., Salmon E., de Leon M.J., Mielke R., Cummings J.L., Kowell A.P., Gambhir S.S., Hoh C.K., and Phelps M.E. Positron Emission Tomography in Evaluation of Dementia: Regional Brain Metabolism and Long-term Outcome vol. 286 (2001) 2120-2127
7. Atamna H., and Frey II W.H. Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer's disease. Mitochondrion 7 (2007) 297-310
8. Nicholls D. Mitochondrial bioenergetics, aging, and aging-related disease. Science Aging Knowledge Environment 2002 (2002) e12
9. Biessels G.J., and Kappelle L.J. Increased risk of Alzheimer's disease in Type II diabetes: insulin resistance of the brain or insulin-induced amyloid pathology?. Biochemical Society Transactions 33 (2005) 1041-1044
10. Petit-Taboue M.C., Landeau B., Desson J.F., Desgranges B., and Baron J.C. Effects of healthy aging on the regional cerebral metabolic rate of glucose assessed with statistical parametric mapping. NeuroImage 7 (1998) 176-184
11. Small G.W., Bookheimer S.Y., Thompson P.M., Cole G.M., Huang S.C., Kepe V., and Barrio J.R. Current and future uses of neuroimaging for cognitively impaired patients. Lancet Neurology 7 (2008) 161-172
12. Yong S.W., Yoon J.K., An Y.S., and Lee P.H. A comparison of cerebral glucose metabolism in Parkinson's disease. Parkinson's disease dementia and dementia with Lewy bodies vol. 14 (2007) 1357-1362
13. Cadenas E. Mitochondrial free radical production and cell signaling. Molecular Aspects of Medicine 25 (2004) 17-26
14. Giulivi C., Poderoso J.J., and Boveris A. Production of nitric oxide by mitochondria. Journal of Biological Chemistry 273 (1998) 11038-11043
15. P. Storz, Reactive oxygen species-mediated mitochondria-to-nucleus signaling: a key to aging and radical-caused diseases, Sci STKE 2006 (2006) re3.
16. Giorgio M., Trinei M., Migliaccio E., and Pelicci P.G. Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals?. Nature Reviews 8 (2007) 722-728
17. Jang Y.C., and Remmen V.H. The mitochondrial theory of aging: insight from transgenic and knockout mouse models. Experimental Gerontology 44 (2009) 256-260
18. Borras C., Stvolinsky S., Lopez-Grueso R., Fedorova T., Gambini J., Boldyrev A., and Vina J. Low in vivo brain glucose consumption and high oxidative stress in accelerated aging. FEBS Letters 583 (2009) 2287-2293
19. Navarro A., and Boveris A. The mitochondrial energy transduction system and the aging process. American Journal of Physiology. Cell Physiology 292 (2007) C670-686
20. Boveris A., and Navarro A. Brain mitochondrial dysfunction in aging. IUBMB Life 60 (2008) 308-314
21. Han D., Antunes F., Daneri F., and Cadenas E. Mitochondrial superoxide anion production and release into intermembrane space. Methods in Enzymology 349 (2002) 271-280
22. Turrens J.F., and Boveris A. Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. Biochemical Journal 191 (1980) 421-427
23. 2 by overexpressing peroxiredoxin 3 improves glucose tolerance in mice. Aging Cell 7 (2008) 866-878
24. Rebrin I., Kamzalov S., and Sohal R.S. Effects of age and caloric restriction on glutathione redox state in mice. Free radical biology & medicine 35 (2003) 626-635
25. Butterfield D.A., Howard B., Yatin S., Koppal T., Drake J., Hensley K., Aksenov M., Aksenova M., Subramaniam R., Varadarajan S., Harris-White M.E., Pedigo Jr. N.W., and Carney J.M. Elevated oxidative stress in models of normal brain aging and Alzheimer's disease. Life Sciences 65 (1999) 1883-1892
26. Calabrese V., Sultana R., Scapagnini G., Guagliano E., Sapienza M., Bella R., Kanski J., Pennisi G., Mancuso C., Stella A.M., and Butterfield D.A. Nitrosative stress, cellular stress response, and thiol homeostasis in patients with Alzheimer's disease. Antioxidants & Redox Signaling 8 (2006) 1975-1986
27. Jones D.P., Mody Jr. V.C., Carlson J.L., Lynn M.J., and Sternberg Jr. P. Redox analysis of human plasma allows separation of pro-oxidant events of aging from decline in antioxidant defenses. Free Radical Biology & Medicine 33 (2002) 1290-1300
28. Newman S.F., Sultana R., Perluigi M., Coccia R., Cai J., Pierce W.M., Klein J.B., Turner D.M., and Butterfield D.A. An increase in S-glutathionylated proteins in the Alzheimer's disease inferior parietal lobule, a proteomics approach. Journal of Neuroscience Research 85 (2007) 1506-1514
29. Ferguson M., Mockett R.J., Shen Y., Orr W.C., and Sohal R.S. Age-associated decline in mitochondrial respiration and electron transport in Drosophila melanogaster. Biochemical Journal 390 (2005) 501-511
30. Navarro A., López-Cepero J.M., Bández M.J., Sánchez-Pino M.-J., Gómez C., Cadenas E., and Boveris A. Hippocampal mitochondrial dysfunction in rat aging. American Journal of Physiology, Regulatory, Integrative and Comparative Physiology 294 (2008) R501-R509
31. Boveris A., Costa L.E., and Cadenas E. The mitochondrial production of oxygen radicals and cellular aging. In: Cadenas E., and Packer L. (Eds). Understanding the Process of Aging. The Roles of Mitochondria, Free Radicals, and Antioxidants (1999), Marcel Dekker, Inc., New York 1-16
32. Navarro A., and Boveris A. Rat brain and liver mitochondria develop oxidative stress and lose enzymatic activities on aging. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 287 (2004) R1244-1249
33. Davey G.P., Peuchen S., and Clark J.B. Energy thresholds in brain mitochondria. Potential involvement in neurodegeneration. Journal of Biological Chemistry 273 (1998) 12753-12757
34. Davey G.P., Canevari L., and Clark J.B. Threshold effects in synaptosomal and nonsynaptic mitochondria from hippocampal CA1 and paramedian neocortex brain regions. Journal of Neurochemistry 69 (1997) 2564-2570
35. Schagger H., and Pfeiffer K. The ratio of oxidative phosphorylation complexes I-V in bovine heart mitochondria and the composition of respiratory chain supercomplexes. The Journal of Biological Chemistry 276 (2001) 37861-37867
36. D.L. Nelson, M.M. Cox, Lehninger Principles of Biochemistry, Fifth Edition ed., W.H.Freemand and Company, New York, 2008.
37. Rydstrom J., and Mitochondrial N.A.D.P.H. transhydrogenase and disease. Biochimica et Biophysica Acta 1757 (2006) 721-726
38. Yarian C.S., Toroser D., and Sohal R.S. Aconitase is the main functional target of aging in the citric acid cycle of kidney mitochondria from mice. Mechanisms of Ageing and Development 127 (2006) 79-84
39. Zhou Q., Lam P.Y., Han D., and Cadenas E. c-Jun N-terminal kinase regulates mitochondrial bioenergetics by modulating pyruvate dehydrogenase activity in primary cortical neurons. Journal of Neurochemistry 104 (2008) 325-335
40. Zhou Q., Lam P.Y., Han D., and Cadenas E. Activation of c-Jun-N-terminal kinase and decline of mitochondrial pyruvate dehydrogenase activity during brain aging. FEBS letters 583 (2009) 1132-1140
41. Bubber P., Haroutunian V., Fisch G., Blass J.P., and Gibson G.E. Mitochondrial abnormalities in Alzheimer brain: mechanistic implications. Annals of Neurology 57 (2005) 695-703
42. Gibson G.E., Sheu K.F., and Blass J.P. Abnormalities of mitochondrial enzymes in Alzheimer disease. Journal of Neural Transmission 105 (1998) 855-870
43. Lucas D.T., and Szweda L.I. Declines in mitochondrial respiration during cardiac reperfusion: age-dependent inactivation of alpha-ketoglutarate dehydrogenase. Proceedings of the National Academy of Sciences of the United States of America 96 (1999) 6689-6693
44. Tretter L., and Adam-Vizi V. Inhibition of Krebs cycle enzymes by hydrogen peroxide: a key role of [alpha]-ketoglutarate dehydrogenase in limiting NADH production under oxidative stress. Journal of Neuroscience 20 (2000) 8972-8979
45. Berg J.M., Tymocko J.L., and Stryer L. Chapter 17: the Citric Acid Cycle, Biochemistry (2002), W.H.Freeman and Company, United States of America
46. Schafer F.Q., and Buettner G.R. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radical Biology & Medicine 30 (2001) 1191-1212
47. Patenaude A., Ven Murthy M.R., and Mirault M.E. Mitochondrial thioredoxin system: effects of TrxR2 overexpression on redox balance, cell growth, and apoptosis. The Journal of Biological Chemistry 279 (2004) 27302-27314
48. Han D., Canali R., Rettori D., and Kaplowitz N. Effect of glutathione depletion on sites and topology of superoxide and hydrogen peroxide production in mitochondria. Molecular Pharmacology 64 (2003) 1136-1144
49. Finkel T., and Holbrook N.J. Oxidants, oxidative stress and the biology of ageing. Nature 408 (2000) 239-247
50. Lin M.T., and Beal M.F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443 (2006) 787-795
51. Han D., Hanawa N., Saberi B., and Kaplowitz N. Mechanisms of liver injury. III. Role of glutathione redox status in liver injury. American Journal of Physiology: Gastrointestinal and Liver Physiology 291 (2006) G1-7
52. Martensson J., Lai J.C., and Meister A. High-affinity transport of glutathione is part of a multicomponent system essential for mitochondrial function. Proceedings of the National Academy of Sciences of the United States of America 87 (1990) 7185-7189
53. Hurd T.R., Costa N.H., Dahm C.c., Beer S.M., Brown S.E., Filipovska A., and Murphy M.P. Glutathionylation of mitochondrial proteins. Antioxidants and Redox Signalig 7 (2005) 999-1010
54. Liu L., Hausladen A., Zeng M., Que L., Heitman J., and Stamler J.S. A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans. Nature 410 (2001) 490-494
55. Dalle-Donne I., Milzani A., Gagliano N., Colombo R., Giustarini D., and Rossi R. Molecular mechanisms and potential clinical significance of S-glutathionylation. Antioxidants & Redox Signaling 10 (2008) 445-473
56. Vlamis-Gardikas A., and Holmgren A. Thioredoxin and glutaredoxin isoforms. Methods in Enzymology 347 (2002) 286-296
57. Mustacich D., and Powis G. Thioredoxin reductase. Biochemical Journal 346 Pt 1 (2000) 1-8
58. Rebrin I., Forster M.J., and Sohal R.S. Effects of age and caloric intake on glutathione redox state in different brain regions of C57BL/6 and DBA/2 mice. Brain Research 1127 (2007) 10-18
59. Jones D.P. Radical-free biology of oxidative stress. American Journal of Physiology. Cell Physiology 295 (2008) C849-868
60. Miranda-Vizuete A., Damdimopoulos A.E., and Spyrou G. The mitochondrial thioredoxin system. Antioxidants & Redox Signaling 2 (2000) 801-810
61. Zhang H., Go Y.M., and Jones D.P. Mitochondrial thioredoxin-2/peroxiredoxin-3 system functions in parallel with mitochondrial GSH system in protection against oxidative stress. Archives of Biochemistry and Biophysics 465 (2007) 119-126
62. Hofmann B., Hecht H.J., and Flohe L. Peroxiredoxins. Biological Chemistry 383 (2002) 347-364
63. Rohrbach S., Gruenler S., Teschner M., and Holtz J. The thioredoxin system in aging muscle: key role of mitochondrial thioredoxin reductase in the protective effects of caloric restriction?. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 291 (2006) R927-R935
64. Bunik V.I. 2-Oxo acid dehydrogenase complexes in redox regulation. European Journal of Biochemistry/FEBS 270 (2003) 1036-1042
65. Johansson C., Lillig C.H., and Holmgren A. Human mitochondrial glutaredoxin reduces S-glutathionylated proteins with high affinity accepting electrons from either glutathione or thioredoxin reductase. The Journal of Biological Chemistry 279 (2004) 7537-7543
66. Jones D.P. Disruption of mitochondrial redox circuitry in oxidative stress. Chem. Biol. Interact. 163 (2006) 38-53
67. Starkov A.A., Polster B.M., and Fiskum G. Regulation of hydrogen peroxide production by brain mitochondria by calcium and Bax. Journal of Neurochemistry 83 (2002) 220-228
68. Han D., Ybanez M.D., Ahmadi S., Yeh K., and Kaplowitz N. Redox regulation of tumor necrosis factor signaling. Antioxidants & Redox Signaling 11 (2009) 2245-2263
69. Klatt P., and Lamas S. Regulation of protein function by S-glutathiolation in response to oxidative and nitrosative stress. European Journal of Biochemistry/FEBS 267 (2000) 4928-4944
70. Janssen-Heininger Y.M., Mossman B.T., Heintz N.H., Forman H.J., Kalyanaraman B., Finkel T., Stamler J.S., Rhee S.G., and van der Vliet A. Redox-based regulation of signal transduction: principles, pitfalls, and promises. Free Radical Biology & Medicine 45 (2008) 1-17
71. Boveris A., Cadenas E., and Stoppani A.O.M. Role of ubiquinone in the mitochondrial generation of hydrogen peroxide. Biochemical Journal 156 (1976) 435-444
72. Cadenas E., Boveris A., Ragan C.I., and Stoppani A.O.M. Production of superoxide radicals and hydrogen peroxide by NADH-ubiquinone reductase and ubiquinol-cytochrome c reductase from beef-heart mitochondria. Archives of Biochemistry and Biophysics 180 (1977) 248-257
73. Han D., Williams E., and Cadenas E. Mitochondrial respiratory chain-dependent generation of superoxide anion and its release into the intermembrane space. Biochemical Journal 353 (2001) 411-416
74. Han D., Antunes F., Canali R., Rettori D., and Cadenas E. Voltage-dependent anion channels control the release of the superoxide anion from mitochondria to cytosol. Journal of Biological Chemistry 278 (2003) 5557-5563
75. Inarrea P., Moini H., Rettori D., Han D., Martinez J., Garcia I., Fernandez-Vizarra E., Iturralde M., and Cadenas E. Redox activation of mitochondrial intermembrane space Cu, Zn-superoxide dismutase. Biochemical Journal 387 (2005) 203-209
76. Sanz A., Caro P., Ibanez J., Gomez J., Gredilla R., and Barja G. Dietary restriction at old age lowers mitochondrial oxygen radical production and leak at complex I and oxidative DNA damage in rat brain. Journal of Bioenergetics and Biomembranes 37 (2005) 83-90
77. Taylor E.R., Hurrell F., Shannon R.J., Lin T.K., Hirst J., and Murphy M.P. Reversible glutathionylation of complex I increases mitochondrial superoxide formation. The Journal of Biological Chemistry 278 (2003) 19603-19610
78. Andersen J.K. Oxidative stress in neurodegeneration: cause or consequence. Nature Reviews Neuroscience 5 (2004) S18-S25
79. Hauptmann N., Grimsby J., Shih J.C., and Cadenas E. The metabolism of tyramine by monoamine oxidase A/B causes oxidative damage to mitochondrial DNA. Archives of Biochemistry and Biophysics 335 (1996) 295-304
80. Hauptmann N., Grimsby J., Shih J.C., and Cadenas E. The metabolism of tyramine by monoamine oxidase A/B causes oxidative damage to mitochondrial DNA. Archives of Biochemistry and Biophysics 335 (1996) 295-304
81. Radi R., Cassina A., and Hodara R. Nitric oxide and peroxynitrite interactions with mitochondria. Biological Chemistry 383 (2002) 401-409
82. Boyd C.S., and Cadenas E. Nitric oxide and cell signaling pathways in mitochondrial dependent apoptosis. Biological Chemistry 383 (2002) 411-423
83. Bates T.E., Loesch A., Burnstock G., and Clark J.B. Immunocytochemical evidence for a mitochondrially located nitric oxide synthase in brain and liver. Biochemical and Biophysical Research Communications 213 (1995) 896-900
84. Riobó N., Melani M., Sanjuan N., Fiszman M.L., Gravielle M.C., Carreras M.C., Cadenas E., and Poderoso J.J. The modulation of mitochondrial nitric oxide synthase activity in rat brain development. Journal of Biological Chemistry 277 (2002) 42447-42455
85. Valdez L.B., and Boveris A. Mitochondrial nitric oxide synthase, a voltage-dependent enzyme, is responsible for nitric oxide diffusion to cytosol. Frontiers in Bioscience 12 (2007) 1210-1219
86. Persichini T., Mazzone V., Polticelli F., Moreno S., Venturini G., Clementi E., and Colasanti M. Mitochondrial type I nitric oxide synthase physically interacts with cytochrome c oxidase. Neuroscience Letters 384 (2005) 254-259
87. Boveris A., Valdez L.B., Zaobornyj T., and Bustamante J. Mitochondrial metabolic states regulate nitric oxide and hydrogen peroxide diffusion to the cytosol. Biochimica et Biophysica Acta 1757 (2006) 535-542
88. Antunes F., Boveris A., and Cadenas E. On the biologic role of the reaction of NO with oxidized cytochrome c oxidase. Antioxidants & Redox Signalling 9 (2007) 1569-1579
89. Antunes F., Boveris A., and Cadenas E. On the mechanism and biology of cytochrome oxidase inhibition by nitric oxide. Proceedings of the National Academy of Sciences of the United States of America 101 (2004) 16774-16779
90. Brookes P.S., Levonen A.L., Shiva S., Sarti P., and Darley-Usmar V.M. Mitochondria: regulators of signal transduction by reactive oxygen and nitrogen species. Free Radical Biology & Medicine 33 (2002) 755-764
91. Riobó N.A., Clementi E., Melani M., Boveris A., Cadenas E., Moncada S., and Poderoso J.J. Nitric oxide inhibits mitochondrial NADH-ubiquinone reductase activity through the formation of peroxynitrite. Biochemical Journal 359 (2001) 139-145
92. Boveris A., and Cadenas E. Cellular sources and steady-state levels of reactive oxygen species. In: Clerch L.B., and Massaro D.J. (Eds). Oxygen, Gene Expression, and Cellular Function (1997), Marcel Dekker, New York 1-25
93. Bharath S., and Andersen J.K. Glutathione depletion in a midbrain-derived immortalized dopaminergic cell line results in limited tyrosine nitration of mitochondrial complex I subunits: implications for Parkinson's disease. Antioxidants & Redox Signalling 7 (2005) 900-910
94. 2 detoxification in in vivo conditions. Free Radical Biology & Medicine 33 (2002) 1260-1267
95. Martinez-Ruiz A., and Lamas S. S-nitrosylation: a potential new paradigm in signal transduction. Cardiovascular Research 62 (2004) 43-52
96. Ying W. NAD+/NADH and NADP+/NADPH in cellular functions and cell death: regulation and biological consequences. Antioxidants & Redox Signaling 10 (2008) 179-206
97. Vogel R., Wiesinger H., Hamprecht B., and Dringen R. The regeneration of reduced glutathione in rat forebrain mitochondria identifies metabolic pathways providing the NADPH required. Neuroscience Letters 275 (1999) 97-100
98. Olausson T., Fjellstrom O., Meuller J., and Rydstrom J. Molecular biology of nicotinamide nucleotide transhydrogenase-a unique proton pump. Biochimica et Biophysica Acta 1231 (1995) 1-19
99. Forsmark-Andree P., Persson B., Radi R., Dallner G., and Ernster L. Oxidative modification of nicotinamide nucleotide transhydrogenase in submitochondrial particles: effect of endogenous ubiquinol. Archives of Biochemistry and Biophysics 336 (1996) 113-120
100. Horbinski C., and Chu C.T. Kinase signaling cascades in the mitochondrion: a matter of life or death. Free Radical Biology & Medicine 38 (2005) 2-11
101. Nemoto S., Takeda K., Yu Z.X., Ferrans V.J., and Finkel T. Role for mitochondrial oxidants as regulators of cellular metabolism. Molecular and Cellular Biology 20 (2000) 7311-7318
102. Hanawa N., Shinohara M., Saberi B., Gaarde W.A., Han D., and Kaplowitz N. Role of JNK translocation to mitochondria leading to inhibition of mitochondria bioenergetics in acetaminophen-induced liver injury. The Journal of Biological Chemistry 283 (2008) 13565-13577
103. Schroeter H., Boyd C.S., Ahmed R., Spencer J.P., Duncan R.F., Rice-Evans C., and Cadenas E. c-Jun N-terminal kinase (JNK)-mediated modulation of brain mitochondria function: new target proteins for JNk signaling in mitochondrion-dependent apoptosis. Biochemical Journal 372 (2003) 359-369
104. Prins M.L. Cerebral metabolic adaptation and ketone metabolism after brain injury. Journal of Cerebral Blood Flow and Metabolism 28 (2008) 1-16
105. Han D., Canali R., Garcia J., Aguilera R., Gallaher T.K., and Cadenas E. Sites and mechanisms of aconitase inactivation by peroxynitrite: modulation by citrate and glutathione. Biochemistry 44 (2005) 11986-11996
106. Fugere N.A., Ferrington D.A., and Thompson L.V. Protein nitration with aging in the rat semimembranosus and soleus muscles. The Journals of Gerontology 61 (2006) 806-812
107. Bulteau A.L., Lundberg K.C., Ikeda-Saito M., Isaya G., and Szweda L.I. Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion. Proceedings of the National Academy of Sciences of the United States of America 102 (2005) 5987-5991
108. Nulton-Persson A.C., Starke D.W., Mieyal J.J., and Szweda L.I. Reversible inactivation of alpha-ketoglutarate dehydrogenase in response to alterations in the mitochondrial glutathione status. Biochemistry 42 (2003) 4235-4242
109. Applegate M.A., Humphries K.M., and Szweda L.I. Reversible inhibition of alpha-ketoglutarate dehydrogenase by hydrogen peroxide: glutathionylation and protection of lipoic acid. Biochemistry 47 (2008) 473-478
110. Rossignol R., Faustin B., Rocher C., Malgat M., Mazat J.-P., and Letellier T. Mitochondrial threshold effects. Biochemical Journal 370 (2003) 751-762
111. Clementi E., Brown G.C., Feelisch M., and Moncada S. Persistent inhibition of cell respiration by nitric oxide: crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione. Proceedings of the National Academy of Sciences of the United States of America 95 (1998) 7631-7636
112. Chinta S.J., and Andersen J.K. Reversible inhibition of mitochondrial complex I activity following chronic dopaminergic glutathione depletion in vitro: implications for Parkinson's disease. Free Radical Biology & Medicine 41 (2006) 1442-1448
113. Yadava N., and Nicholls D.G. Spare respiratory capacity rather than oxidative stress regulates glutamate excitotoxicity after partial respiratory inhibition of mitochondrial complex I with rotenone. Journal of Neuroscience 27 (2007) 7310-7317
114. Porcelli A.M., Angelin A., Ghelli A., Mariani E., Martinuzzi A., Carelli V., Petronilli V., Bernardi P., and Rugolo M. Respiratory complex I dysfunction due to mitochondrial DNA mutations shifts the voltage threshold for opening of the permeability transition pore toward resting levels. The Journal of Biological Chemistry 284 (2009) 2045-2052
115. Boveris A., Costa L.E., Poderoso J.J., Carreras M.C., and Cadenas E. Regulation of mitochondrial respiration by oxygen and nitric oxide. Annals of the New York Academy of Sciences 899 (2000) 121-135
116. Moncada S., and Erusalimsky J.D. Does nitric oxide modulate mitochondrial energy generation and apoptosis?. Nature Reviews 3 (2002) 214-220
117. Wang X., Perez E., Liu R., Yan L.J., Mallet R.T., and Yang S.H. Pyruvate protects mitochondria from oxidative stress in human neuroblastoma SK-N-SH cells. Brain Research 1132 (2007) 1-9
118. Desagher S., Glowinski J., and Premont J. Pyruvate protects neurons against hydrogen peroxide-induced toxicity. Journal of Neuroscience 17 (1997) 9060-9067
119. Frenzel J., Richter J., and Eschrich K. Pyruvate protects glucose-deprived Muller cells from nitric oxide-induced oxidative stress by radical scavenging. Glia 52 (2005) 276-288
120. Alvarez G., Ramos M., Ruiz F., Satrustegui J., and Bogonez E. Pyruvate protection against beta-amyloid-induced neuronal death: role of mitochondrial redox state. Journal of Neuroscience Research 73 (2003) 260-269
121. Wang X., Takata T., Sakurai T., and Yokono K. Different effects of monocarboxylates on neuronal survival and beta-amyloid toxicity. European Journal of Neuroscience 26 (2007) 2142-2150
122. Pellerin L. How astrocytes feed hungry neurons. Molecular Neurobiology 32 (2005) 59-72
123. Hashimoto T., Hussien R., Cho H.S., Kaufer D., and Brooks G.A. Evidence for the mitochondrial lactate oxidation complex in rat neurons: demonstration of an essential component of brain lactate shuttles. PLoS ONE 3 (2008) e2915
124. Yang H., Yang T., Baur J.A., Perez E., Matsui T., Carmona J.J., Lamming D.W., Souza-Pinto N.C., Bohr V.A., Rosenzweig A., de Cabo R., Sauve A.A., and Sinclair D.A. Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival. Cell 130 (2007) 1095-1107
125. Packer L., Tritschler H.J., and Wessel K. Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radical Biology & Medicine 22 (1997) 359-378
126. Dodd S., Dean O., Copolov D.L., Malhi G.S., and Berk M. N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility. Expert Opinion on Biological Therapy 8 (2008) 1955-1962
127. Korotchkina L.G. P. M.S., Pyruvate dehydrogenase complex regulation and lipoic acid. In: Patel M.S., and Packer L. (Eds). Lipoic Acid: Energy Production, Antioxidant Activity, and Health Effects (2008), CRC Press, Boca Raton 149-165
128. Prehn J.H., Karkoutly C., Nuglisch J., Peruche B., and Krieglstein J. Dihydrolipoate reduces neuronal injury after cerebral ischemia. Journal of Cerebral Blood Flow and Metabolism 12 (1992) 78-87
129. Jayalakshmi K., Sairam M., Singh S.B., Sharma S.K., Ilavazhagan G., and Banerjee P.K. Neuroprotective effect of N-acetyl cysteine on hypoxia-induced oxidative stress in primary hippocampal culture. Brain Research 1046 (2005) 97-104
130. Bielarczyk H., Gul S., Ronowska A., Bizon-Zygmanska D., Pawelczyk T., and Szutowicz A. RS-alpha-lipoic acid protects cholinergic cells against sodium nitroprusside and amyloid-beta neurotoxicity through restoration of acetyl-CoA level. Journal of Neurochemistry 98 (2006) 1242-1251
131. Lovell M.A., Xie C., Xiong S., and Markesbery W.R. Protection against amyloid beta peptide and iron/hydrogen peroxide toxicity by alpha lipoic acid. Journal of Alzheimers Disease 5 (2003) 229-239
132. Muller U., and Krieglstein J. Prolonged pretreatment with alpha-lipoic acid protects cultured neurons against hypoxic, glutamate-, or iron-induced injury. Journal of Cerebral Blood Flow and Metabolism 15 (1995) 624-630
133. Gow A.J., Chen Q., Gole M., Themistocleous M., Lee V.M., and Ischiropoulos H. Two distinct mechanisms of nitric oxide-mediated neuronal cell death show thiol dependency. American Journal of Physiology. Cell Physiology 278 (2000) C1099-1107
134. Olivieri G., Baysang G., Meier F., Muller-Spahn F., Stahelin H.B., Brockhaus M., and Brack C. N-acetyl-L-cysteine protects SHSY5Y neuroblastoma cells from oxidative stress and cell cytotoxicity: effects on beta-amyloid secretion and tau phosphorylation. Journal of Neurochemistry 76 (2001) 224-233
135. Zhang L., Xing G.Q., Barker J.L., Chang Y., Maric D., Ma W., Li B.S., and Rubinow D.R. Alpha-lipoic acid protects rat cortical neurons against cell death induced by amyloid and hydrogen peroxide through the Akt signalling pathway. Neuroscience Letters 312 (2001) 125-128
136. Atkuri K.R., Mantovani J.J., Herzenberg L.A., and Herzenberg L.A. N-Acetylcysteine-a safe antidote for cysteine/glutathione deficiency. Current Opinion in Pharmacology 7 (2007) 355-359
137. Han D., Handelman G., Marcocci L., Sen C.K., Roy S., Kobuchi H., Tritschler H.J., Flohe L., and Packer L. Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. BioFactors (Oxford, England) 6 (1997) 321-338
138. Han D., Hamilton R.T., and Lam P. l (2008), Packer, Modulation of Cellular Redox and Metabolic Status by Lipoic Acid pp. 293-314
139. Kensler T.W., Wakabayashi N., and Biswal S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annual Review of Pharmacology and Toxicology 47 (2007) 89-116
140. Shenvi S.V., Smith E.J., and Hagen T.M. Transcriptional regulation of rat gamma-glutamate cysteine ligase catalytic subunit gene is mediated through a distal antioxidant response element. Pharmacological Research 60 (2009) 229-236
141. Suh J.H., Shenvi S.V., Dixon B.M., Liu H., Jaiswal A.K., Liu R.M., and Hagen T.M. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proceedings of the National Academy of Sciences of the United States of America 101 (2004) 3381-3386
142. Han D., Hamilton R.T., Lam P.Y., and Packer L. Modulation of cellular redox and metabolic status by lipoic acid. In: Patel M.S., and Packer L. (Eds). Lipoic Acid: Energy Production, Antioxidant Activity, and Health Effects (2008), CRC Press, Boca Raton 293-314
143. Haramaki N., Han D., Handelman G.J., Tritschler H.J., and Packer L. Cytosolic and mitochondrial systems for NADH- and NADPH-dependent reduction of alpha-lipoic acid. Free Radical Biology & Medicine 22 (1997) 535-542
144. Henderson S.T. Ketone bodies as a therapeutic for Alzheimer's disease. Neurotherapeutics 5 (2008) 470-480
145. Costantini L.C., Barr L.J., Vogel J.L., and Henderson S.T. Hypometabolism as a therapeutic target in Alzheimer's disease. BMC Neuroscience 9 Suppl 2 (2008) S16
146. Kashiwaya Y., Takeshima T., Mori N., Nakashima K., Clarke K., and Veech R.L. D-beta-hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease. Proceedings of the National Academy of Sciences of the United States of America 97 (2000) 5440-5444
147. Tieu K., Perier C., Caspersen C., Teismann P., Wu D.C., Yan S.D., Naini A., Vila M., Jackson-Lewis V., Ramasamy R., and Przedborski S. D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. Journal of Clinical Investigation 112 (2003) 892-901
148. Martinez M., Hernandez A.I., and Martinez N. N-Acetylcysteine delays age-associated memory impairment in mice: role in synaptic mitochondria. Brain Research 855 (2000) 100-106
149. Panigrahi M., Sadguna Y., Shivakumar B.R., Kolluri S.V., Roy S., Packer L., and Ravindranath V. alpha-Lipoic acid protects against reperfusion injury following cerebral ischemia in rats. Brain Research 717 (1996) 184-188
150. Chng H.T., New L.S., Neo A.H., Goh C.W., Browne E.R., and Chan E.C. Distribution study of orally administered lipoic acid in rat brain tissues. Brain Research 1251 (2009) 80-86
151. Kim M.S., Park J.Y., Namkoong C., Jang P.G., Ryu J.W., Song H.S., Yun J.Y., Namgoong I.S., Ha J., Park I.S., Lee I.K., Viollet B., Youn J.H., Lee H.K., and Lee K.U. Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase. Nature Medicine 10 (2004) 727-733
152. Suh J.H., Wang H., Liu R.M., Liu J., and Hagen T.M. (R)-alpha-lipoic acid reverses the age-related loss in GSH redox status in post-mitotic tissues: evidence for increased cysteine requirement for GSH synthesis. Archives of Biochemistry and Biophysics 423 (2004) 126-135
153. Suh J.H., Moreau R., Heath S.H., and Hagen T.M. Dietary supplementation with (R)-alpha-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex. Redox Report 10 (2005) 52-60
154. Hagen T.M., Liu J., Lykkesfeldt J., Wehr C.M., Ingersoll R.T., Vinarsky V., Bartholomew J.C., and Ames B.N. Feeding acetyl-l-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proceedings of the National Academy of Sciences of the United States of America 99 (2002) 1870-1875
155. Hagen T.M., Ingersoll R.T., Lykkesfeldt J., Liu J., Wehr C.M., Vinarsky V., Bartholomew J.C., and Ames A.B. (R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. Faseb Journal 13 (1999) 411-418
156. Lykkesfeldt J., Hagen T.M., Vinarsky V., and Ames B.N. Age-associated decline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes-reversal with (R)-alpha-lipoic acid supplementation. Faseb Journal 12 (1998) 1183-1189
157. Diesel B., Kulhanek-Heinze S., Holtje M., Brandt B., Holtje H.D., Vollmar A.M., and Kiemer A.K. Alpha-lipoic acid as a directly binding activator of the insulin receptor: protection from hepatocyte apoptosis. Biochemistry 46 (2007) 2146-2155
158. Moini H., Tirosh O., Park Y.C., Cho K.J., and Packer L. R-alpha-lipoic acid action on cell redox status, the insulin receptor, and glucose uptake in 3T3-L1 adipocytes. Archives of Biochemistry and Biophysics 397 (2002) 384-391
159. Farr S.A., Poon H.F., Dogrukol-Ak D., Drake J., Banks W.A., Eyerman E., Butterfield D.A., and Morley J.E. The antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice. Journal of Neurochemistry 84 (2003) 1173-1183
160. Quinn J.F., Bussiere J.R., Hammond R.S., Montine T.J., Henson E., Jones R.E., and Stackman Jr. R.W. Chronic dietary alpha-lipoic acid reduces deficits in hippocampal memory of aged Tg2576 mice. Neurobiology Aging 28 (2007) 213-225
161. Shenk J.C., Liu J., Fischbach K., Xu K., Puchowicz M., Obrenovich M.E., Gasimov E., Alvarez L.M., Ames B.N., Lamanna J.C., and Aliev G. The effect of acetyl-l-carnitine and R-alpha-lipoic acid treatment in ApoE4 mouse as a model of human Alzheimer's disease. Journal of the Neurological Sciences 283 (2009) 199-206
162. Hager K., Kenklies M., McAfoose J., Engel J., and Munch G. Alpha-lipoic acid as a new treatment option for Alzheimer's disease-a 48 months follow-up analysis. Journal of Neural Transmission. Supplementum (2007) 189-193
163. Zhang W.J., Wei H., Hagen T., and Frei B. Alpha-lipoic acid attenuates LPS-induced inflammatory responses by activating the phosphoinositide 3-kinase/Akt signaling pathway. Proceedings of the National Academy of Sciences of the United States of America 104 (2007) 4077-4082
164. Rogers J., Mastroeni D., Leonard B., Joyce J., and Grover A. Neuroinflammation in Alzheimer's disease and Parkinson's disease: are microglia pathogenic in either disorder?. International Review of Neurobiology 82 (2007) 235-246
165. DiPatre P.L., and Gelman B.B. Microglial cell activation in aging and Alzheimer disease: partial linkage with neurofibrillary tangle burden in the hippocampus. Journal of Neuropathology and Experimental Neurology 56 (1997) 143-149
166. Prins M., and Hovda D. The effects of age and ketogenic diet on local cerebral metabolic rates of glucose after controlled cortical impact injury in rats. Journal of Neurotrauma 26 (2009) 1083-1093
167. Kadish I., Thibault O., Blalock E.M., Chen K.C., Gant J.C., Porter N.M., and Landfield P.W. Hippocampal and cognitive aging across the lifespan: a bioenergetic shift precedes and increased cholesterol trafficking parallels memory impairment. Journal of Neuroscience 29 (2009) 1805-1816
168. Nehlig A., and Pereira de Vasconcelos A. Glucose and ketone body utilization by the brain of neonatal rats. Progress in Neurobiology 40 (1993) 163-221
169. Lund T.M., Risa O., Sonnewald U., Schousboe A., and Waagepetersen H.S. Availability of neurotransmitter glutamate is diminished when beta-hydroxybutyrate replaces glucose in cultured neurons. Journal of Neurotrauma 110 (2009) 80-91
170. Pelletier A., Tardif A., Gingras M.H., Chiasson J.L., and Coderre L. Chronic exposure to ketone bodies impairs glucose uptake in adult cardiomyocytes in response to insulin but not vanadate: the role of PI3-K. Molecular and Cellular Biochemistry 296 (2007) 97-108