Oxidative stress induced mitochondrial failure and vascular hypoperfusion as a key initiator for the development of alzheimer disease

Pharmaceuticals

Volumn 3, Issue 1, 2010, Pages 158-187

  Aliev, Gjumrakch ^a,b,c   Palacios, Hector H ^d   Gasimov, Eldar ^e   Obrenovich, Mark E ^f   Morales, Ludis ^b   Leszek, Jerzy ^g   Bragin, Valentin ^c   Herrera, Arturo Solís ^h   Gokhman, Dmitry ⁱ  

^a University of Atlanta   (United States)

^b PONTIFICIA UNIVERSIDAD JAVERIANA   (Colombia)

^c Stress Relief and Memory Training Center   (United States)

^d University of San Antonio   (United States)

^e AZERBAIJAN MEDICAL UNIVERSITY   (Azerbaijan)

^f CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^g WROCLAW MEDICAL UNIVERSITY   (Poland)

^h Zona Centro   (Mexico)

ⁱ UNIVERSITY OF TEXAS AT SAN ANTONIO   (United States)

Author keywords

Alzheimer disease; Antioxidants; Hypometabolism; Metabolism; Mitochondria; Neurodegeneration; Oxidative stress

Indexed keywords

ADENOSINE TRIPHOSPHATE; AMYLOID BETA PROTEIN; ANTIINFLAMMATORY AGENT; ANTIOXIDANT; APOLIPOPROTEIN E4; ENDOTHELIAL NITRIC OXIDE SYNTHASE; ENDOTHELIN 1; HERBACEOUS AGENT; HYPOCHOLESTEROLEMIC AGENT; INDUCIBLE NITRIC OXIDE SYNTHASE; LEVACECARNINE; MITOCHONDRIAL DNA; NEURONAL NITRIC OXIDE SYNTHASE; NITRIC OXIDE SYNTHASE; OXYGEN RADICAL; REACTIVE OXYGEN METABOLITE; SUPEROXIDE; THIOCTIC ACID; VASOACTIVE AGENT;

AGING; ALZHEIMER DISEASE; BIOACCUMULATION; BLOOD BRAIN BARRIER; BLOOD VESSEL TONE; BRAIN BIOPSY; BRAIN ISCHEMIA; BRAIN MICROCIRCULATION; BRAIN PERFUSION; CELL ULTRASTRUCTURE; CEREBROVASCULAR ACCIDENT; CIGARETTE SMOKING; CLINICAL FEATURE; DEGENERATIVE DISEASE; DEMENTIA; DISEASE ASSOCIATION; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG MECHANISM; ENZYME REGULATION; GENE EXPRESSION; HUMAN; MICROVASCULATURE; MITOCHONDRIAL MEMBRANE POTENTIAL; NERVE CELL LESION; NEUROPATHOLOGY; NONHUMAN; OXIDATIVE STRESS; PROGNOSIS; PROTEIN FUNCTION; RESPIRATION CONTROL; RESPIRATORY CHAIN; REVIEW; RISK FACTOR; SIGNAL TRANSDUCTION; VASCULAR ENDOTHELIUM;

EID: 77951964504     PISSN: None     EISSN: 14248247     Source Type: Journal    
DOI: 10.3390/ph3010158     Document Type: Review

References (172)

1. Aliev, G.; Smith, M.A.; Seyidov, D.; Neal, M.L.; Lamb, B.T.; Nunomura, A.; Gasimov, E.K.; Vinters, H.V.; Perry, G.; LaManna, J.C.; Friedland, R.P. The role of oxidative stress in the pathophysiology of cerebrovascular lesions in Alzheimer's disease. Brain Pathol. 2002, 12, 21-35.
2. Aliev, G.; Gasimov, E.; Obrenovich, M.E.; Fischbach, K.; Shenk, J.C.; Smith, M.A.; Perry, G. Atherosclerotic lesions and mitochondria DNA deletions in brain microvessels: implication in the pathogenesis of Alzheimer's disease. Vasc. Health Risk Manag. 2008, 4, 721-730.
3. Aliev, G.; Palacios, H.H.; Walrafen, B.; Lipsitt, A.E.; Obrenovich, M.E.; Morales, L. Brain mitochondria as a primary target in the development of treatment strategies for Alzheimer disease. Int. J. Biochem. Cell Biol. 2009, 41, 1989-2004.
4. De la Torre, J.C. Cerebrovascular and cardiovascular pathology in Alzheimer's disease. Int. Rev. Neurobiol. 2009, 84, 35-48.
5. Kalaria, R.N. The blood-brain barrier and cerebrovascular pathology in Alzheimer's disease. Ann. N. Y. Acad. Sci. 1999, 893, 113-125.
6. Kalaria, R.N. The role of cerebral ischemia in Alzheimer's disease. Neurobiol. Aging 2000, 21, 321-330.
7. Aliev, G.; Palacios, H.H.; Lipsitt, A.E.; Fischbach, K.; Lamb, B.T.; Obrenovich, M.E.; Morales, L.; Gasimov, E.; Bragin, V. Nitric oxide as an initiator of brain lesions during the development of Alzheimer disease. Neurotox. Res. 2009, 16, 293-305.
8. Aliev, G. Is non-genetic Alzheimer's disease a vascular disorder with neurodegenerative consequences? J. Alzheimer's Dis. 2002, 4, 513-516.
9. Aliev, G.; Cirillo, R.; Salvatico, E.; Paro, M.; Prosdocimi, M. Changes in vessel ultrastructure during ischemia and reperfusion of rabbit hindlimb: implications for therapeutic intervention. Microvasc. Res. 1993, 46, 65-76.
10. De la Torre, J.C. Alzheimer disease as a vascular disorder: nosological evidence. Stroke 2002, 33, 1152-1162.
11. Aliev, G.; Obrenovich, M.E.; Reddy, V.P.; Shenk, J.C.; Moreira, P.I.; Nunomura, A.; Zhu, X.; Smith, M.A.; Perry, G. Antioxidant therapy in Alzheimer's disease: theory and practice. Mini Rev. Med. Chem. 2008, 8, 1395-1406.
12. Lum, H.; Roebuck, K.A. Oxidant stress and endothelial cell dysfunction. Am. J. Physiol. Cell Physiol. 2001, 280, C719-C741.
13. Coyle, J.T.; Puttfarcken, P. Oxidative stress, glutamate, and neurodegenerative disorders. Science 1993, 262, 689-695.
14. Perry, G.; Smith, M.A.; McCann, C.E.; Siedlak, S.L.; Jones, P.K.; Friedland, R.P. Cerebrovascular muscle atrophy is a feature of Alzheimer's disease. Brain Res. 1998, 791, 63-66.
15. Smith, M.A.; Perry, G.; Richey, P.L.; Sayre, L.M.; Anderson, V.E.; Beal, M.F.; Kowall, N. Oxidative damage in Alzheimer's. Nature 1996, 382, 120-121.
16. Smith, M.A.; Petot, G.J.; Perry, G. Commentary: Diet and Oxidative Stress: A Novel Synthesis of Epidemiological Data on Alzheimer's Disease. Alzheimer's Dis. Rev. 1997, 2, 58-60.
17. Smith, M.A.; Richey Harris, P.L.; Sayre, L.M.; Beckman, J.S.; Perry, G. Widespread peroxynitrite-mediated damage in Alzheimer's disease. J. Neurosci. 1997, 17, 2653-2657.
18. Smith, M.A.; Rottkamp, C.A.; Nunomura, A.; Raina, A.K.; Perry, G. Oxidative stress in Alzheimer's disease. Biochim. Biophys. Acta 2000, 1502, 139-144.
19. Smith, M.A.; Sayre, L.M.; Perry, G. Is Alzheimer's a Disease of Oxidative Stress? Alzheimer's Dis. Rev. 1996, 1, 63-67.
20. Smith, M.A.; Vasak, M.; Knipp, M.; Castellani, R.J.; Perry, G. Dimethylargininase, a nitric oxide regulatory protein, in Alzheimer disease. Free Radic. Biol. Med. 1998, 25, 898-902.
21. Lovell, M.A.; Xie, C.; Markesbery, W.R. Decreased glutathione transferase activity in brain and ventricular fluid in Alzheimer's disease. Neurology 1998, 51, 1562-1566.
22. Prasad, M.R.; Lovell, M.A.; Yatin, M.; Dhillon, H.; Markesbery, W.R. Regional membrane phospholipid alterations in Alzheimer's disease. Neurochem. Res. 1998, 23, 81-88.
23. Prelli, F.; Castano, E.M.; van Duinen, S.G.; Bots, G.T.; Luyendijk, W.; Frangione, B. Different processing of Alzheimer's beta-protein precursor in the vessel wall of patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type. Biochem. Biophys. Res. Commun. 1988, 151, 1150-1155.
24. Markesbery, W.R. Oxidative stress hypothesis in Alzheimer's disease. Free Radic. Biol. Med. 1997, 23, 134-147.
25. Markesbery, W.R.; Carney, J.M. Oxidative alterations in Alzheimer's disease. Brain Pathol. 1999, 9, 133-146.
26. Mecocci, P.; Beal, M.F.; Cecchetti, R.; Polidori, M.C.; Cherubini, A.; Chionne, F.; Avellini, L.; Romano, G.; Senin, U. Mitochondrial membrane fluidity and oxidative damage to mitochondrial DNA in aged and AD human brain. Mol. Chem. Neuropathol. 1997, 31, 53-64.
27. Mecocci, P.; MacGarvey, U.; Beal, M.F. Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease. Ann. Neurol. 1994, 36, 747-751.
28. Mecocci, P.; MacGarvey, U.; Kaufman, A.E.; Koontz, D.; Shoffner, J.M.; Wallace, D.C.; Beal, M.F. Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain. Ann. Neurol. 1993, 34, 609-616.
29. Nunomura, A.; Perry, G.; Aliev, G.; Hirai, K.; Takeda, A.; Balraj, E.K.; Jones, P.K.; Ghanbari, H.; Wataya, T.; Shimohama, S.; Chiba, S.; Atwood, C.S.; Petersen, R.B.; Smith, M.A. Oxidative damage is the earliest event in Alzheimer disease. J. Neuropathol. Exp. Neurol. 2001, 60, 759-767.
30. Nunomura, A.; Perry, G.; Hirai, K.; Aliev, G.; Takeda, A.; Chiba, S.; Smith, M.A. Neuronal RNA oxidation in Alzheimer's disease and Down's syndrome. Ann. N. Y. Acad. Sci. 1999, 893, 362-364.
31. Nunomura, A.; Perry, G.; Pappolla, M.A.; Wade, R.; Hirai, K.; Chiba, S.; Smith, M.A. RNA oxidation is a prominent feature of vulnerable neurons in Alzheimer's disease. J. Neurosci. 1999, 19, 1959-1964.
32. Perry, G.; Nunomura, A.; Hirai, K.; Takeda, A.; Aliev, G.; Smith, M.A. Oxidative damage in Alzheimer's disease: the metabolic dimension. Int. J. Dev. Neurosci. 2000, 18, 417-421.
33. Sayre, L.M.; Zelasko, D.A.; Harris, P.L.; Perry, G.; Salomon, R.G.; Smith, M.A. 4-Hydroxynonenal-derived advanced lipid peroxidation end products are increased in Alzheimer's disease. J. Neurochem. 1997, 68, 2092-2097.
34. Smith, M.A.; Taneda, S.; Richey, P.L.; Miyata, S.; Yan, S.D.; Stern, D.; Sayre, L.M.; Monnier, V.M.; Perry, G. Advanced Maillard reaction end products are associated with Alzheimer's disease pathology. Proc. Natl. Acad. Sci, USA 1994, 91, 5710-5714.
35. Cirillo, R.; Aliev, G.; Hornby, E.J.; Prosdocimi, M. Endothelium as a therapeutical target in peripheral occlusive arterial diseases: consideration for pharmacological interventions. Pharmacol. Res. 1994, 29, 293-311.
36. Cirillo, R.; Salvatico, E.; Aliev, G.; Prosdocimi, M. Effect of cloricromene during ischemia and reperfusion of rabbit hindlimb: evidence for an involvement of leukocytes in reperfusionmediated tissue and vascular injury. J. Cardiovasc. Pharmacol. 1992, 20, 969-975.
37. Granger, D.N.; Benoit, J.N.; Suzuki, M.; Grisham, M.B. Leukocyte adherence to venular endothelium during ischemia-reperfusion. Am. J. Physiol. 1989, 257, G683-688.
38. Sala, A.; Aliev, G.M.; Rossoni, G.; Berti, F.; Buccellati, C.; Burnstock, G.; Folco, G.; Maclouf, J. Morphological and functional changes of coronary vasculature caused by transcellular biosynthesis of sulfidopeptide leukotrienes in isolated heart of rabbit. Blood 1996, 87, 1824-1832.
39. Salvatico, E.; Aliev, G.M.; Novello, D.; Prosdocimi, M. Functional depression of isolated perfused rat heart mediated by activated leukocytes: protective effect of cloricromene. J. Cardiovasc. Pharmacol. 1994, 24, 638-647.
40. Matz, R.L.; Schott, C.; Stoclet, J.C.; Andriantsitohaina, R. Age-related endothelial dysfunction with respect to nitric oxide, endothelium-derived hyperpolarizing factor and cyclooxygenase products. Physiol. Res. 2000, 49, 11-18.
41. Aliev, G.; Burnstock, G. Watanabe rabbits with heritable hypercholesterolaemia: a model of atherosclerosis. Histol. Histopathol. 1998, 13, 797-817.
42. Stewart-Lee, A.L.; Ferns, G.A.; Anggard, E.E. Differences in onset of impaired endothelial responses and in effects of vitamin E in the hypercholesterolemic rabbit carotid and renal arteries. J. Cardiovasc. Pharmacol. 1995, 25, 906-913.
43. Price, J.M.; Sutton, E.T.; Hellermann, A.; Thomas, T. beta-Amyloid induces cerebrovascular endothelial dysfunction in the rat brain. Neurol. Res. 1997, 19, 534-538.
44. Iadecola, C.; Zhang, F.; Niwa, K.; Eckman, C.; Turner, S.K.; Fischer, E.; Younkin, S.; Borchelt, D.R.; Hsiao, K.K.; Carlson, G.A. SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein. Nat. Neurosci. 1999, 2, 157-161.
45. Niwa, K.; Carlson, G.A.; Iadecola, C. Exogenous a beta1-40 reproduces cerebrovascular alterations resulting from amyloid precursor protein overexpression in mice. J. Cereb. Blood Flow Metab. 2000, 20, 1659-1668.
46. Grammas, P.; Moore, P.; Weigel, P.H. Microvessels from Alzheimer's disease brains kill neurons in vitro. Am. J. Pathol. 1999, 154, 337-342.
47. Mao, P.; Reddy, P.H. Is multiple sclerosis a mitochondrial disease? Biochim. Biophys. Acta 2009, 1802, 66-79.
48. Acuna-Castroviejo, D.; Martin, M.; Macias, M.; Escames, G.; Leon, J.; Khaldy, H.; Reiter, R.J. Melatonin, mitochondria, and cellular bioenergetics. J. Pineal Res. 2001, 30, 65-74.
49. Castellani, R.; Hirai, K.; Aliev, G.; Drew, K.L.; Nunomura, A.; Takeda, A.; Cash, A.D.; Obrenovich, M.E.; Perry, G.; Smith, M.A. Role of mitochondrial dysfunction in Alzheimer's disease. J. Neurosci. Res. 2002, 70, 357-360.
50. Fiskum, G.; Murphy, A.N.; Beal, M.F. Mitochondria in neurodegeneration: acute ischemia and chronic neurodegenerative diseases. J. Cereb. Blood Flow Metab. 1999, 19, 351-369.
51. Schulz, J.B.; Matthews, R.T.; Klockgether, T.; Dichgans, J.; Beal, M.F. The role of mitochondrial dysfunction and neuronal nitric oxide in animal models of neurodegenerative diseases. Mol. Cell Biochem. 1997, 174, 193-197.
52. Vancova, O.; Baciak, L.; Kasparova, S.; Kucharska, J.; Palacios, H.H.; Horecky, J.; Aliev, G. In vivo and in vitro assessment of brain bioenergetics in aging rats. JCMM 2009, doi:10.1111/j.1582-4934.
53. Hirai, K.; Aliev, G.; Nunomura, A.; Fujioka, H.; Russell, R.L.; Atwood, C.S.; Johnson, A.B.; Kress, Y.; Vinters, H.V.; Tabaton, M.; Shimohama, S.; Cash, A.D.; Siedlak, S.L.; Harris, P.L.; Jones, P.K.; Petersen, R.B.; Perry, G.; Smith, M.A. Mitochondrial abnormalities in Alzheimer's disease. J. Neurosci. 2001, 21, 3017-3023.
54. Horecky, J.; Baciak, L.; Kasparova, S.; Pacheco, G.; Aliev, G.; Vancova, O. Minimally invasive surgical approach for three-vessel occlusion as a model of vascular dementia in the rat-brain bioenergetics assay. J. Neurol. Sci. 2009, 283, 178-181.
55. Beckman, K.B.; Ames, B.N. The free radical theory of aging matures. Physiol. Rev. 1998, 78, 547-581.
56. Beckman, K.B.; Ames, B.N. Mitochondrial aging: open questions. Ann. N.Y. Acad. Sci. 1998, 854, 118-127.
57. Beckman, K.B.; Ames, B.N. Endogenous oxidative damage of mtDNA. Mutat. Res. 1999, 424, 51-58.
58. Wallace, D.C. Mitochondrial diseases in man and mouse. Science 1999, 283, 1482-1488.
59. Aliev, G.; Smith, M.A.; Vinters, H.; Johnson, A.B.; Nunomura, A.; Perry, G. Mitochondria abnormalities mark vulnerable neurons in Alzheimer's disease. J. Neuropathol. Exper. Neurol. 1999, 58, 511.
60. Beal, M.F. Aging, energy, and oxidative stress in neurodegenerative diseases. Ann. Neurol. 1995, 38, 357-366.
61. Bonilla, E.; Tanji, K.; Hirano, M.; Vu, T.H.; DiMauro, S.; Schon, E.A. Mitochondrial involvement in Alzheimer's disease. Biochim. Biophys. Acta 1999, 1410, 171-182.
62. Aliev, G.; Smith, M.A.; Obrenovich, M.E.; de la Torre, J.C.; Perry, G. Role of vascular Hypoperfusion-induced oxidative stress and mitochondria failure in the pathogenesis of Alzheimer's disease. Neurotox. Res. 2003, 5, 491-504.
63. Al-Abdulla, N.A.; Martin, L.J. Apoptosis of retrogradely degenerating neurons occurs in association with the accumulation of perikaryal mitochondria and oxidative damage to the nucleus. Am. J. Pathol. 1998, 153, 447-456.
64. Wallace, D.C. Mitochondrial DNA in aging and disease. Sci. Am. 1997, 277, 40-47.
65. Cormier, A.; Morin, C.; Zini, R.; Tillement, J.P.; Lagrue, G. In vitro effects of nicotine on mitochondrial respiration and superoxide anion generation. Brain Res. 2001, 900, 72-79.
66. Reddy, P.H. Role of mitochondria in neurodegenerative diseases: mitochondria as a therapeutic target in Alzheimer's disease. C.N.S. Spectr. 2009, 14, 8-13, 16-18.
67. Aliyev, A.; Chen, S.G.; Seyidova, D.; Smith, M.A.; Perry, G.; de la Torre, J.; Aliev, G. Mitochondria DNA deletions in atherosclerotic hypoperfused brain microvessels as a primary target for the development of Alzheimer's disease. J. Neurol. Sci. 2005, 229/230, 285-292.
68. De Jong, G.I.; De Vos, R.A.; Steur, E.N.; Luiten, P.G. Cerebrovascular hypoperfusion: a risk factor for Alzheimer's disease? Animal model and postmortem human studies. Ann. N.Y. Acad. Sci. 1997, 826, 56-74.
69. De la Torre, J.C. Hemodynamic consequences of deformed microvessels in the brain in Alzheimer's disease. Ann. N.Y. Acad. Sci. 1997, 826, 75-91.
70. Friston, K.J.; Frackowiak, R.S. Cerebral function in aging and Alzheimer's disease: the role of PET. Electroencephalogr. Clin. Neurophysiol. Suppl. 1991, 42, 355-365.
71. Kumar, A.; Schapiro, M.B.; Haxby, J.V.; Grady, C.L.; Friedland, R.P. Cerebral metabolic and cognitive studies in dementia with frontal lobe behavioral features. J. Psychiatr. Res. 1990, 24, 97-109.
72. Galle, J.; Bengen, J.; Schollmeyer, P.; Wanner, C. Impairment of endothelium-dependent dilation in rabbit renal arteries by oxidized lipoprotein(a). Role of oxygen-derived radicals. Circulation 1995, 92, 1582-1589.
73. de la Torre, J.C.; Stefano, G.B. Evidence that Alzheimer's disease is a microvascular disorder: the role of constitutive nitric oxide. Brain Res. Brain Res. Rev. 2000, 34, 119-136.
74. Meguro, K.; Blaizot, X.; Kondoh, Y.; Le Mestric, C.; Baron, J.C.; Chavoix, C. Neocortical and hippocampal glucose hypometabolism following neurotoxic lesions of the entorhinal and perirhinal cortices in the non-human primate as shown by PET. Implications for Alzheimer's disease. Brain 1999, 122 (Pt. 8), 1519-1531.
75. Jagust, W.J.; Friedland, R.P.; Budinger, T.F.; Koss, E.; Ober, B. Longitudinal studies of regional cerebral metabolism in Alzheimer's disease. Neurology 1988, 38, 909-912.
76. de la Torre, J.C. Pathophysiology of neuronal energy crisis in Alzheimer's disease. Neurodegener. Dis. 2008, 5, 126-132.
77. de la Torre, J.C. Alzheimer disease as a vascular disorder: nosological evidence. Stroke 2002, 33, 1152-1162.
78. De la Torre, J.C. Critically attained threshold of cerebral hypoperfusion: can it cause Alzheimer's disease? Ann. N.Y. Acad. Sci. 2000, 903, 424-436.
79. De la Torre, J.C. Alzheimer's disease prevalence can be lowered with non-invasive testing. J. Alzheimer's Dis. 2008, 14, 353-359.
80. Hofman, A.; Ott, A.; Breteler, M.M.; Bots, M.L.; Slooter, A.J.; van Harskamp, F.; van Duijn, C.N.; Van Broeckhoven, C.; Grobbee, D.E. Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study. Lancet 1997, 349, 151-154.
81. Weinbrecht, P.; Longmuir, I.; Knopp, J.; Mills, M. Cerebral microcirculatory changes during exposure to hypoxia. Adv. Exp. Med. Biol. 1987, 215, 259-263.
82. Mironov, V.; Hritz, M.A.; LaManna, J.C.; Hudetz, A.G.; Harik, S.I. Architectural alterations in rat cerebral microvessels after hypobaric hypoxia. Brain Res. 1994, 660, 73-80.
83. Chavez, J.C.; Agani, F.; Pichiule, P.; LaManna, J.C. Expression of hypoxia-inducible factor-1 alpha in the brain of rats during chronic hypoxia. J. Appl. Physiol. 2000, 89, 1937-1942.
84. Stewart, P.A.; Isaacs, H.; LaManna, J.C.; Harik, S.I. Ultrastructural concomitants of hypoxia-induced angiogenesis. Acta Neuropathol. (Berl.) 1997, 93, 579-584.
85. LaManna, J.C.; Boehm, K.D.; Mironov, V.; Hudetz, A.G.; Hritz, M.A.; Yun, J.K.; Harik, S.I. Increased basic fibroblastic growth factor mRNA in the brains of rats exposed to hypobaric hypoxia. Adv. Exp. Med. Biol. 1994, 361, 497-502.
86. Harik, N.; Harik, S.I.; Kuo, N.T.; Sakai, K.; Przybylski, R.J.; LaManna, J.C. Time-course and reversibility of the hypoxia-induced alterations in cerebral vascularity and cerebral capillary glucose transporter density. Brain Res. 1996, 737, 335-338.
87. Zhu, X.; Smith, M.A.; Perry, G.; Aliev, G. Mitochondrial failures in Alzheimer's disease. Am. J. Alzheimer's Dis. Other Demen. 2004, 19, 345-352.
88. Aliev, G.; Smith, M.A.; Turmaine, M.; Neal, M.L.; Zimina, T.V.; Friedland, R.P.; Perry, G.; LaManna, J.C.; Burnstock, G. Atherosclerotic lesions are associated with increased immunoreactivity for inducible nitric oxide synthase and endothelin-1 in thoracic aortic intimal cells of hyperlipidemic Watanabe rabbits. Exp. Mol. Pathol. 2001, 71, 40-54.
89. Shi, J.; Perry, G.; Berridge, M.S.; Aliev, G.; Siedlak, S.L.; Smith, M.A.; LaManna, J.C.; Friedland, R.P. Labeling of cerebral amyloid beta deposits in vivo using intranasal basic fibroblast growth factor and serum amyloid P component in mice. JNM 2002, 43, 1044-1051.
90. Bednar, M.M.; Raymond, S.; McAuliffe, T.; Lodge, P.A.; Gross, C.E. The role of neutrophils and platelets in a rabbit model of thromboembolic stroke. Stroke 1991, 22, 44-50.
91. Chen, H.; Chopp, M.; Zhang, Z.G.; Garcia, J.H. The effect of hypothermia on transient middle cerebral artery occlusion in the rat. J. Cereb. Blood Flow Metab. 1992, 12, 621-628.
92. Olah, L.; Wecker, S.; Hoehn, M. Relation of apparent diffusion coefficient changes and metabolic disturbances after 1 hour of focal cerebral ischemia and at different reperfusion phases in rats. J. Cereb. Blood Flow Metab. 2001, 21, 430-439.
93. Dietrich, W.D.; Busto, R.; Ginsberg, M.D. Cerebral endothelial microvilli: formation following global forebrain ischemia. J. Neuropathol. Exp. Neurol. 1984, 43, 72-83.
94. Fischer, E.G.; Ames 3d, A. Studies on mechanisms of impairment of cerebral circulation following ischemia: effect of hemodilution and perfusion pressure. Stroke 1972, 3, 538-542.
95. Wade, J.G.; Amtorp, O.; Sorensen, S.C. No-flow state following cerebral ischemia. Role of increase in potassium concentration in brain interstitial fluid. Arch. Neurol. 1975, 32, 381-384.
96. Cada, A.; de la Torre, J.C.; Gonzalez-Lima, F. Chronic cerebrovascular ischemia in aged rats: effects on brain metabolic capacity and behavior. Neurobiol. Aging 2000, 21, 225-233.
97. Marletta, M.A. Nitric oxide synthase: aspects concerning structure and catalysis. Cell 1994, 78, 927-930.
98. Moncada, S.; Higgs, E.A. Molecular mechanisms and therapeutic strategies related to nitric oxide. FASEB J. 1995, 9, 1319-1330.
99. Moncada, S.; Palmer, R.M.; Higgs, E.A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol. Rev. 1991, 43, 109-142.
100. Crow, J.P.; Ye, Y.Z.; Strong, M.; Kirk, M.; Barnes, S.; Beckman, J.S. Superoxide dismutase catalyzes nitration of tyrosines by peroxynitrite in the rod and head domains of neurofilament L. J. Neurochem. 1997, 69, 1945-1953.
101. Dawson, V.L.; Brahmbhatt, H.P.; Mong, J.A.; Dawson, T.M. Expression of inducible nitric oxide synthase causes delayed neurotoxicity in primary mixed neuronal-glial cortical cultures. Neuropharmacology 1994, 33, 1425-1430.
102. Dawson, V.L.; Dawson, T.M. Nitric oxide in neuronal degeneration. Proc. Soc. Exp. Biol. Med. 1996, 211, 33-40.
103. Dawson, V.L.; Dawson, T.M.; London, E.D.; Bredt, D.S.; Snyder, S.H. Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc. Natl. Acad. Sci. USA 1991, 88, 6368-6371.
104. Michel, T.; Feron, O. Nitric oxide synthases: which, where, how, and why? J. Clin. Invest. 1997, 100, 2146-2152.
105. Wever, R.M.; Luscher, T.F.; Cosentino, F.; Rabelink, T.J. Atherosclerosis and the two faces of endothelial nitric oxide synthase. Circulation 1998, 97, 108-112.
106. Xia, Y.; Dawson, V.L.; Dawson, T.M.; Snyder, S.H.; Zweier, J.L. Nitric oxide synthase generates superoxide and nitric oxide in arginine-depleted cells leading to peroxynitrite-mediated cellular injury. Proc. Natl. Acad. Sci. USA 1996, 93, 6770-6774.
107. Ignarro, L.J. Biosynthesis and metabolism of endothelium-derived nitric oxide. Annu. Rev. Pharmacol. Toxicol. 1990, 30, 535-560.
108. Stamler, J.S. Redox signaling: nitrosylation and related target interactions of nitric oxide. Cell 1994, 78, 931-936.
109. Robinson, L.J.; Weremowicz, S.; Morton, C.C.; Michel, T. Isolation and chromosomal localization of the human endothelial nitric oxide synthase (NOS3) gene. Genomics 1994, 19, 350-357.
110. Sessa, W.C. The nitric oxide synthase family of proteins. J. Vasc. Res. 1994, 31, 131-143.
111. Stuehr, D.J. Structure-function aspects in the nitric oxide synthases. Annu. Rev. Pharmacol. Toxicol. 1997, 37, 339-359.
112. Morris, S.M., Jr.; Billiar, T.R. New insights into the regulation of inducible nitric oxide synthesis. Am. J. Physiol. 1994, 266, E829-E839.
113. Bates, T.E.; Loesch, A.; Burnstock, G.; Clark, J.B. Immunocytochemical evidence for a mitochondrially located nitric oxide synthase in brain and liver. Biochem. Biophys. Res. Commun. 1995, 213, 896-900.
114. Bates, T.E.; Loesch, A.; Burnstock, G.; Clark, J.B. Mitochondrial nitric oxide synthase: a ubiquitous regulator of oxidative phosphorylation? Biochem. Biophys. Res. Commun.1996, 218, 40-44.
115. Dawson, D.A. Nitric oxide and focal cerebral ischemia: multiplicity of actions and diverse outcome. Cerebrovasc. Brain Metab. Rev. 1994, 6, 299-324.
116. Bredt, D.S.; Snyder, S.H. Nitric oxide: a physiologic messenger molecule. Annu. Rev. Biochem. 1994, 63, 175-195.
117. Faraci, F.M.; Brian, J.E., Jr. Nitric oxide and the cerebral circulation. Stroke 1994, 25, 692-703.
118. Almeida, A.; Bolanos, J.P.; Medina, J.M. Nitric oxide mediates glutamate-induced mitochondrial depolarization in rat cortical neurons. Brain Res. 1999, 816, 580-586.
119. Beckman, J.S. The double-edged role of nitric oxide in brain function and superoxide-mediated injury. J. Dev. Physiol. 1991, 15, 53-59.
120. Beckman, J.S.; Beckman, T.W.; Chen, J.; Marshall, P.A.; Freeman, B.A. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc. Natl. Acad. Sci. USA 1990, 87, 1620-1624.
121. Beckman, J.S.; Chen, J.; Ischiropoulos, H.; Crow, J.P. Oxidative chemistry of peroxynitrite. Methods Enzymol. 1994, 233, 229-240.
122. Cazevieille, C.; Muller, A.; Meynier, F.; Bonne, C. Superoxide and nitric oxide cooperation in hypoxia/reoxygenation-induced neuron injury. Free Radic. Biol. Med. 1993, 14, 389-395.
123. Radi, R.; Beckman, J.S.; Bush, K.M.; Freeman, B.A. Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide. J. Biol. Chem. 1991, 266, 4244-4250.
124. Lafon-Cazal, M.; Pietri, S.; Culcasi, M.; Bockaert, J. NMDA-dependent superoxide production and neurotoxicity. Nature 1993, 364, 535-537.
125. Faraci, F.M. Role of endothelium-derived relaxing factor in cerebral circulation: large arteries vs. microcirculation. Am. J. Physiol. 1991, 261, H1038-H1042.
126. Fabricius, M.; Lauritzen, M. Examination of the role of nitric oxide for the hypercapnic rise of cerebral blood flow in rats. Am. J. Physiol. 1994, 266, H1457-H1464.
127. Iadecola, C. Does nitric oxide mediate the increases in cerebral blood flow elicited by hypercapnia? Proc. Natl. Acad. Sci. USA 1992, 89, 3913-3916.
128. Buisson, A.; Margaill, I.; Callebert, J.; Plotkine, M.; Boulu, R.G. Mechanisms involved in the neuroprotective activity of a nitric oxide synthase inhibitor during focal cerebral ischemia. J. Neurochem. 1993, 61, 690-696.
129. Buisson, A.; Plotkine, M.; Boulu, R.G. The neuroprotective effect of a nitric oxide inhibitor in a rat model of focal cerebral ischaemia. Br. J. Pharmacol. 1992, 106, 766-767.
130. Samadani, A.F.; Dawson, T.M.; Dawson, V.L. Nitric oxide synthase in model of focal ischemia. Stroke 1997, 28, 1283-1288.
131. Hamada, Y.; Hayakawa, T.; Hattori, H.; Mikawa, H. Inhibitor of nitric oxide synthesis reduces hypoxic-ischemic brain damage in the neonatal rat. Pediatr. Res. 1994, 35, 10-14.
132. Iadecola, C.; Li, J.; Ebner, T.J.; Xu, X. Nitric oxide contributes to functional hyperemia in cerebellar cortex. Am. J. Physiol. 1995, 268, R1153-R1162.
133. Iadecola, C.; Zhang, F.; Casey, R.; Clark, H.B.; Ross, M.E. Inducible nitric oxide synthase gene expression in vascular cells after transient focal cerebral ischemia. Stroke 1996, 27, 1373-1380.
134. Iadecola, C.; Zhang, F.; Xu, S.; Casey, R.; Ross, M.E. Inducible nitric oxide synthase gene expression in brain following cerebral ischemia. J. Cereb. Blood Flow Metab. 1995, 15, 378-384.
135. Nakashima, M.N.; Yamashita, K.; Kataoka, Y.; Yamashita, Y.S.; Niwa, M. Time course of nitric oxide synthase activity in neuronal, glial, and endothelial cells of rat striatum following focal cerebral ischemia. Cell Mol. Neurobiol. 1995, 15, 341-349.
136. Wang, Q.; Pelligrino, D.A.; Baughman, V.L.; Koenig, H.M.; Albrecht, R.F. The role of neuronal nitric oxide synthase in regulation of cerebral blood flow in normocapnia and hypercapnia in rats. J Cereb. Blood Flow Metab. 1995, 15, 774-778.
137. Garthwaite, J.; Beaumont, P.S. Excitatory amino acid receptors in the parallel fibre pathway in rat cerebellar slices. Neurosci. Lett. 1989, 107, 151-156.
138. Hara, H.; Huang, P.L.; Panahian, N.; Fishman, M.C.; Moskowitz, M.A. Reduced brain edema and infarction volume in mice lacking the neuronal isoform of nitric oxide synthase after transient MCA occlusion. J. Cereb. Blood Flow Metab. 1996, 16, 605-611.
139. Huang, Z.; Huang, P.L.; Panahian, N.; Dalkara, T.; Fishman, M.C.; Moskowitz, M.A. Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase. Science 1994, 265, 1883-1885.
140. Eliasson, M.J.; Sampei, K.; Mandir, A.S.; Hurn, P.D.; Traystman, R.J.; Bao, J.; Pieper, A.; Wang, Z.Q.; Dawson, T.M.; Snyder, S.H.; Dawson, V.L. Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia. Nat. Med. 1997, 3, 1089-1095.
141. Thorns, V.; Hansen, L.; Masliah, E. nNOS expressing neurons in the entorhinal cortex and hippocampus are affected in patients with Alzheimer's disease. Exp. Neurol. 1998, 150, 14-20.
142. Bogumil, R.; Knipp, M.; Fundel, S.M.; Vasak, M. Characterization of dimethylargininase from bovine brain: evidence for a zinc binding site. Biochemistry 1998, 37, 4791-4798.
143. Kimoto, M.; Tsuji, H.; Ogawa, T.; Sasaoka, K. Detection of NG,NG-dimethylarginine dimethylaminohydrolase in the nitric oxide-generating systems of rats using monoclonal antibody. Arch. Biochem. Biophys. 1993, 300, 657-662.
144. Kimoto, M.; Whitley, G.S.; Tsuji, H.; Ogawa, T. Detection of NG,NG-dimethylarginine dimethylaminohydrolase in human tissues using a monoclonal antibody. J. Biochem. (Tokyo) 1995, 117, 237-238.
145. MacAllister, R.J.; Parry, H.; Kimoto, M.; Ogawa, T.; Russell, R.J.; Hodson, H.; Whitley, G.S.; Vallance, P. Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase. Br. J. Pharmacol. 1996, 119, 1533-1540.
146. Beckman, J.S.; Carson, M.; Smith, C.D.; Koppenol, W.H. ALS, SOD and peroxynitrite. Nature 1993, 364, 584.
147. Aliev, G.; Liu, J.; Shenk, J.C.; Fischbach, K.; Pacheco, G.J.; Chen, S.G.; Obrenovich, M.E.; Ward, W.F.; Richardson, A.G.; Smith, M.A.; Gasimov, E.; Perry, G.; Ames, B.N. Neuronal mitochondrial amelioration by feeding acetyl-L-carnitine and lipoic acid to aged rats. JCMM 2009, 2, 320-333.
148. Ames, B.N. Delaying the mitochondrial decay of aging. Ann. N.Y. Acad. Sci. 2004, 1019, 406-411.
149. Ames, B.N. Mitochondrial decay, a major cause of aging, can be delayed. J. Alzheimer's Dis. 2004, 6, 117-121.
150. Ames, B.N.; Liu, J. Delaying the mitochondrial decay of aging with acetyl L-Carnitine. Ann. N.Y. Acad. Sci. 2004, 1033, 108-116.
151. Liu, J.; Head, E.; Gharib, A.M.; Yuan, W.; Ingersoll, R.T.; Hagen, T.M.; Cotman, C.W.; Ames, B.N. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Proc. Natl. Acad. Sci. USA 2002, 99, 2356-2361.
152. Liu, J.; Head, E.; Kuratsune, H.; Cotman, C.W.; Ames, B.N. Comparison of the effects of L-carnitine and acetyl-L-carnitine on carnitine levels, ambulatory activity, and oxidative stress biomarkers in the brain of old rats. Ann. N.Y. Acad. Sci. 2004, 1033, 117-131.
153. Milgram, N.W.; Araujo, J.A.; Hagen, T.M.; Treadwell, B.V.; Ames, B.N. Acetyl-L-Carnitine and alpha-Lipoic acid supplementation of aged beagle dogs improves learning in two landmark discrimination tests. FASEB J. 2007, 21, 3756-3762.
154. 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.; 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. J. Neurol. Sci. 2009, 283, 199-206.
155. Gomez-Pinilla, F. Brain foods: the effects of nutrients on brain function. Nat. Rev. Neurosci. 2008, 9, 568-578.
156. Reddy, P.H. Amyloid beta, mitochondrial structural and functional dynamics in Alzheimer's disease. Exp. Neurol. 2009, 218, 286-292.
157. Liu, J.; Killilea, D.W.; Ames, B.N. Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L-Carnitine and/or R-alpha-Lipoic acid. Proc. Natl. Acad. Sci. USA 2002, 99, 1876-1881.
158. Long, J.; Gao, F.; Tong, L.; Cotman, C.W.; Ames, B.N.; Liu, J. Mitochondrial decay in the brains of old rats: ameliorating effect of alpha-Lipoic acid and acetyl-L-Carnitine. Neurochem. Res. 2009, 34, 755-63.
159. Reddy, P.H.; Beal, M.F. Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease. Trends Mol. Med. 2008, 14, 45-53.
160. Reddy, P.H. Mitochondrial medicine for aging and neurodegenerative diseases. Neuromolecular Med. 2008, 10, 291-315.
161. Reddy, P.H. Amyloid precursor protein-mediated free radicals and oxidative damage: implications for the development and progression of Alzheimer's disease. J. Neurochem. 2006, 96, 1-13.
162. Liu, J.; Atamna, H.; Kuratsune, H.; Ames, B.N. Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites. Ann. N.Y. Acad. Sci. 2002, 959, 133-166.
163. Reid, P.C.; Urano, Y.; Kodama, T.; Hamakubo, T. Alzheimer's disease: cholesterol, membrane rafts, isoprenoids and statins. JCMM 2007, 11, 383-392.
164. Aliev, G.; Shenk, J.C.; Fischbach, K.; Perry, G. Stem cell niches as clinical targets: the future of anti-ischemic therapy? Nat. Clin. Pract. Cardiovasc. Med. 2008, 5, 590-591.
165. Cedazo-Minguez, A. Apolipoprotein E and Alzheimer's disease: molecular mechanisms and therapeutic opportunities. JCMM 2007, 11, 1227-1238.
166. Mas, E.; Dupuy, A.M.; Artero, S.; Portet, F.; Cristol, J.P.; Ritchie, K.; Touchon, J. Functional Vitamin E deficiency in ApoE4 patients with Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 2006, 21, 198-204.
167. Sanchez-Mejia, R.O.; Newman, J.W.; Toh, S.; Yu, G.Q.; Zhou, Y.; Halabisky, B.; Cisse, M.; Scearce-Levie, K.; Cheng, I.H.; Gan, L.; Palop, J.J.; Bonventre, J.V.; Mucke, L. Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer's disease. Nat. Neurosci. 2008, 11, 1311-1318.
168. Anekonda, T.S.; Reddy, P.H. Can herbs provide a new generation of drugs for treating Alzheimer's disease? Brain Res. Brain Res. Rev. 2005, 50, 361-376.
169. Aliev, G.; Castellani, R.J.; Petersen, R.B.; Burnstock, G.; Perry, G.; Smith, M.A. Pathobiology of familial hypercholesterolemic atherosclerosis. J. Submicrosc. Cytol. Pathol. 2004, 36, 225-240.
170. Mahley, R.W.; Weisgraber, K.H.; Huang, Y. Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's disease. Proc. Natl. Acad. Sci. USA 2006, 103, 5644-5651.
171. Reiman, E.M.; Caselli, R.J.; Chen, K.; Alexander, G.E.; Bandy, D.; Frost, J. Declining brain activity in cognitively normal apolipoprotein E epsilon 4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease. Proc. Natl. Acad. Sci. USA 2001, 98, 3334-3339.
172. Aliev, G.; Smith, M.A.; de la Torre, J.C.; Perry, G. Mitochondria as a primary target for vascular hypoperfusion and oxidative stress in Alzheimer's disease. Mitochondrion 2004, 4, 649-663.