Mitochondrion-specific antioxidants as drug treatments for alzheimer disease

CNS and Neurological Disorders - Drug Targets

Volumn 10, Issue 2, 2011, Pages 149-162

  Palacios, Hector H ^a   Yendluri, Bharat B ^a   Parvathaneni, Kalpana ^a   Shadlinski, Vagif B ^b   Obrenovich, Mark E ^c   Leszek, Jerzy ^d   Gokhman, Dmitry ^e   Gasiorowski, Kazimierz ^d   Bragin, Valentin ^f   Aliev, Gjumrakch ^f,g  

^a University of San Antonio   (United States)

^b AZERBAIJAN MEDICAL UNIVERSITY   (Azerbaijan)

^c CLEVELAND STATE UNIVERSITY   (United States)

^d WROCLAW MEDICAL UNIVERSITY   (Poland)

^e UNIVERSITY OF TEXAS AT SAN ANTONIO   (United States)

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

^g University of Atlanta   (United States)

Author keywords

Alzheimer disease; Antioxidants; Mitochondria; Oxidative stress; Reactive oxygen species

Indexed keywords

AMYLOID BETA PROTEIN[1-42]; AMYLOID PRECURSOR PROTEIN; ANTIOXIDANT; APOLIPOPROTEIN E4; ENDOTHELIN 1; LEVACECARNINE; MITOCHONDRIAL DNA; NITRIC OXIDE; PEROXYNITRITE; REACTIVE OXYGEN METABOLITE; THIOCTIC ACID;

ALZHEIMER DISEASE; ANTIOXIDANT ACTIVITY; ARTICLE; BLOOD BRAIN BARRIER; BRAIN BLOOD VESSEL; BRAIN HYPOXIA; BRAIN MITOCHONDRION; CELL ULTRASTRUCTURE; DEGENERATIVE DISEASE; DISEASE ASSOCIATION; DISEASE COURSE; DRUG TARGETING; ENDOTHELIUM CELL; HUMAN; HYPERCHOLESTEROLEMIA; MICROVASCULATURE; NERVE CELL LESION; NEUROLOGIC DISEASE; NEUROPATHOLOGY; NEUROPHARMACOLOGY; NONHUMAN; OXIDATIVE STRESS; RISK FACTOR; TRANSGENIC ANIMAL; VASCULAR DISEASE; VASODILATATION;

EID: 79551673088     PISSN: 18715273     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152711794480474     Document Type: Article

References (94)

1. Thomas, A.J.; Morris, C.M.; Ferrier, I.N.; Kalaria, R.N. Distribution of amyloid beta 42 in relation to the cerebral microvasculature in an elderly cohort with Alzheimer's disease. Ann. NY Acad. Sci., 2000, 903, 83-88.
2. 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(9046), 151-154.
3. Kalaria, R.N. The blood-brain barrier and cerebrovascular pathology in Alzheimer's disease. Ann. NY Acad. Sci., 1999, 893, 113-125.
4. Skoog, I.; Kalaria, R.N.; Breteler, M.M. Vascular factors and Alzheimer disease. Alzheimer Dis. Assoc. Disord., 1999, 13(Suppl 3), S106-S114.
5. Aliev, G.; Burnstock, G. Watanabe rabbits with heritable hypercholesterolaemia: a model of atherosclerosis. Histol. Histopathol., 1998, 13(3), 797-817.
6. 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(1), 65-76.
7. 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.
8. Roses, A.D. On the metabolism of apolipoprotein E and the Alzheimer diseases. Exp. Neurol., 1995, 132(2), 149-156.
9. Aliev, G. Is non-genetic Alzheimer's disease a vascular disorder with neurodegenerative consequences? J. Alzheimers Dis., 2002, 4(6), 513-516.
10. de la Torre, J.C. Alzheimer's disease: how does it start? J. Alzheimers Dis., 2002, 4(6), 497-512.
11. Ellis, R.J.; Olichney, J.M.; Thal, L.J.; Mirra, S.S.; Morris, J.C.; Beekly, D.; Heyman, A. Cerebral amyloid angiopathy in the brains of patients with Alzheimer's disease: the CERAD experience, Part XV. Neurology, 1996, 46(6), 1592-1596.
12. Etiene, D.; Kraft, J.; Ganju, N.; Gomez-Isla, T.; Gemelli, B.; Hyman, B.T.; Hedley-Whyte, E.T.; Wands, J.R.; De La Monte, S.M. Cerebrovascular pathology contributes to the heterogeneity of Alzheimer's disease. J. Alzheimers Dis., 1998, 1(2), 119-134.
13. Kuo, Y.M.; Emmerling, M.R.; Bisgaier, C.L.; Essenburg, A.D.; Lampert, H.C.; Drumm, D.; Roher, A.E. Elevated low-density lipoprotein in Alzheimer's disease correlates with brain abeta 1-42 levels. Biochem. Biophys. Res. Commun., 1998, 252(3), 711-715.
14. 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(1), 21-35.
15. Stewart, P.A.; Hayakawa, K.; Akers, M.A.; Vinters, H.V. A morphometric study of the blood-brain barrier in Alzheimer's disease. Lab. Invest., 1992, 67(6), 734-742.
16. 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. Exp. Neurol., 1999, 58(5), 511.
17. 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(3), 1150-1155.
18. Vinters, H.V.; Miller, B.L.; Pardridge, W.M. Brain amyloid and Alzheimer disease. Ann. Intern. Med., 1988, 109(1), 41-54.
19. Hock, B.J. Jr.; Lamb, B.T. Transgenetic mouse models of Alzheimer's disease.Trends Genet., 2001 17, S7-S12.
20. Jakobovits, A.; Lamb, B.T.; Peterson, K.R. Production of transgenic mice with yeast artificial chromosomes. Methods Mol. Biol., 2000, 136, 435-453.
21. Kulnane, L.S.; Lamb, B.T. Neuropathological characterization of mutant amyloid precursor protein yeast artificial chromosome transgenic mice. Neurobiol. Dis., 2001, 8(6), 982-992.
22. Octave, J.N. The amyloid peptide precursor in Alzheimer's disease. Acta Neurol. Belg., 1995, 95(4), 197-209.
23. Selkoe, D.J. Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer's disease. Annu. Rev. Cell Biol., 1994, 10, 373-403.
24. Crawford, J.G. Alzheimer's disease risk factors as related to cerebral blood flow: additional evidence. Med. Hypotheses, 1998, 50(1), 25-36.
25. Lindahl, B.; Lindahl, U. Amyloid-specific heparan sulfate from human liver and spleen. J. Biol. Chem., 1997, 272(42), 26091-26094.
26. Kisilevsky, R. Amyloid beta threads in the fabric of Alzheimer's disease. Nat. Med., 1998, 4(7), 772-773.
27. Kalaria, R.N. The role of cerebral ischemia in Alzheimer's disease. Neurobiol. Aging, 2000, 21(2), 321-330.
28. Iwamoto, N.; Nishiyama, E.; Ohwada, J.; Arai, H. Distribution of amyloid deposits in the cerebral white matter of the Alzheimer's disease brain: relationship to blood vessels. Acta Neuropathol.(Berl.), 1997, 93(4), 334-340.
29. Kawai, M.; Kalaria, R.N.; Harik, S.I.; Perry, G. The relationship of amyloid plaques to cerebral capillaries in Alzheimer's disease. Am. J. Pathol., 1990, 137(6), 1435-1446.
30. 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(1-2), 63-66.
31. Joachim, C.L.; Morris, J.H.; Selkoe, D.J. Diffuse senile plaques occur commonly in the cerebellum in Alzheimer's disease. Am. J. Pathol., 1989, 135(2), 309-319.
32. Coria, F.; Castano, E.; Prelli, F.; Larrondo-Lillo, M.; van Duinen, S.; Shelanski, M.L.; Frangione, B. Isolation and characterization of amyloid P component from Alzheimer's disease and other types of cerebral amyloidosis. Lab. Invest., 1988, 58(4), 454-458.
33. Tagliavini, F.; Ghiso, J.; Timmers, W.F.; Giaccone, G.; Bugiani, O.; Frangione, B. Coexistence of Alzheimer's amyloid precursor protein and amyloid protein in cerebral vessel walls. Lab. Invest., 1990, 62(6), 761-767.
34. Brunner, F. Interaction of nitric oxide and endothelin-1 in ischemia/reperfusion injury of rat heart. J. Mol. Cell Cardiol., 1997, 29(9), 2363-2374.
35. Lerman, A.; Burnett, J.C. Jr. Intact and altered endothelium in regulation of vasomotion. Circulation, 1992, 86(6 Suppl), III12-III19.
36. Lerman, A.; Hildebrand, F.L. Jr.; Margulies, K.B.; O'Murchu, B.; Perrella, M.A.; Heublein, D.M.; Schwab, T.R.; Burnett, J.C. Jr. Endothelin: a new cardiovascular regulatory peptide. Mayo Clin. Proc., 1990, 65(11), 1441-1455.
37. Lerman, A.; Sandok, E.K.; Hildebrand, F.L. Jr.; Burnett, J.C. Jr. Inhibition of endothelium-derived relaxing factor enhances endothelin-mediated vasoconstriction. Circulation, 1992, 85(5), 1894-1898.
38. Yanagisawa, M.; Kurihara, H.; Kimura, S.; Goto, K.; Masaki, T. A novel peptide vasoconstrictor, endothelin, is produced by vascular endothelium and modulates smooth muscle Ca2+ channels. J. Hypertens. Suppl., 1988, 6(4), S188-S191.
39. Aliev, G.; Shi, J.; Perry, G.; Friedland, R.P.; Lamanna, J.C. Decreased constitutive nitric oxide synthase, but increased inducible nitric oxide synthase and endothelin-1 immunoreactivity in aortic endothelial cells of donryu rats on a cholesterol-enriched diet. Anat. Rec., 2000, 260(1), 16-25.
40. Aliev, G.; Miah, S.; Turmaine, M.; Burnstock, G. An ultrastructural and immunocytochemical study of thoracic aortic endothelium in aged Sprague-Dawley rats. J. Submicrosc. Cytol. Pathol., 1995, 27(4), 477-490.
41. Nelson, J.B.; Hedican, S.P.; George, D.J.; Reddi, A.H.; Piantadosi, S.; Eisenberger, M.A.; Simons, J.W. Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. Nat. Med., 1995, 1(9), 944-949.
42. Aliev, G.; Smith, M.A.; Seyidova, D.; Neal, M.L.; Shi, J.; Loizidou, M.; Turmaine, M.; Friedland, R.P.; Taylor, I.; Burnstock, G.; Perry, G.; Lamanna, J.C. Increased expression of NOS and ET-1 immunoreactivity in human colorectal metastatic liver tumours is associated with selective depression of constitutive NOS immunoreactivity in vessel endothelium. J. Submicrosc. Cytol. Pathol., 2002, 34(1), 37-50.
43. Shankar, A.; Loizidou, M.; Aliev, G.; Fredericks, S.; Holt, D.; Boulos, P.B.; Burnstock, G.; Taylor, I. Raised endothelin 1 levels in patients with colorectal liver metastases. Br. J. Surg., 1998, 85(4), 502-506.
44. Aliev, G.; Ralevic, V.; Burnstock, G. Depression of endothelial nitric oxide synthase but increased expression of endothelin-1 immunoreactivity in rat thoracic aortic endothelium associated with long-term, but not short-term, sympathectomy. Circ. Res., 1996, 79(2), 317-323.
45. 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(1), 40-54.
46. Kulnane, L.S.; Lehman, E.J.; Hock, B.J.; Tsuchiya, K.D.; Lamb, B.T. Rapid and efficient detection of transgene homozygosity by FISH of mouse fibroblasts. Mamm. Genome, 2002, 13(4), 223-226.
47. Lamb, B.T.; Bardel, K.A.; Kulnane, L.S.; Anderson, J.J.; Holtz, G.; Wagner, S.L.; Sisodia, S.S.; Hoeger, E.J. Amyloid production and deposition in mutant amyloid precursor protein and presenilin-1 yeast artificial chromosome transgenic mice. Nat. Neurosci., 1999, 2(8), 695-697.
48. Lamb, B.T.; Call, L.M.; Slunt, H.H.; Bardel, K.A.; Lawler, A.M.; Eckman, C.B.; Younkin, S.G.; Holtz, G.; Wagner, S.L.; Price, D.L.; Sisodia, S.S.; Gearhart, J.D. Altered metabolism of familial Alzheimer's disease-linked amyloid precursor protein variants in yeast artificial chromosome transgenic mice. Hum. Mol. Genet., 1997, 6(9), 1535-1541.
49. Neve, R.L.; Robakis, N.K. Alzheimer's disease: a re-examination of the amyloid hypothesis. Trends Neurosci., 1998, 21(1), 15-19.
50. de la Torre, J.C. Alzheimer disease as a vascular disorder: nosological evidence. Stroke, 2002, 33(4), 1152-1162.
51. Higgins, L.S.; Catalano, R.; Quon, D.; Cordell, B. Transgenic mice expressing human beta-APP751, but not mice expressing beta-APP695, display early Alzheimer's disease-like histopathology. Ann. NY Acad. Sci., 1993, 695, 224-227.
52. Duff, K. Transgenic models for Alzheimer's disease. Neuropathol. Appl. Neurobiol., 1998, 24(2), 101-103.
53. Calhoun, M.E.; Wiederhold, K.H.; Abramowski, D.; Phinney, A.L.; Probst, A.; Sturchler-Pierrat, C.; Staufenbiel, M.; Sommer, B.; Jucker, M. Neuron loss in APP transgenic mice. Nature, 1998, 395(6704), 755-756.
54. Chen, G.; Chen, K.S.; Knox, J.; Inglis, J.; Bernard, A.; Martin, S.J.; Justice, A.; McConlogue, L.; Games, D.; Freedman, S.B.; Morris, R.G. A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer's disease. Nature, 2000, 408(6815), 975-979.
55. Refolo, L.M.; Malester, B.; LaFrancois, J.; Bryant-Thomas, T.; Wang, R.; Tint, G.S.; Sambamurti, K.; Duff, K.; Pappolla, M.A. Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiol. Dis., 2000, 7(4), 321-331.
56. Lin, B.; Ginsberg, M.D.; Busto, R. Hyperglycemic but not normoglycemic global ischemia induces marked early intraneuronal expression of beta-amyloid precursor protein. Brain Res., 2001, 888(1), 107-116.
57. Hsiao, K.; Chapman, P.; Nilsen, S.; Eckman, C.; Harigaya, Y.; Younkin, S.; Yang, F.; Cole, G. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science, 1996, 274(5284), 99-102.
58. 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. J. Nucl. Med., 2002, 43(8), 1044-1051.
59. Shi, J.; Perry, G.; Aliev, G.; Smith, M.A.; Ashe, K.H.; Friedland, R.P. Serum amyloid P is not present in amyloid beta deposits of a transgenic animal model. Neuroreport, 1999, 10(15), 3229-3232.
60. Beach, T.G. Physiologic origins of age-related beta-amyloid deposition. Neurodegener. Dis., 2008, 5(3-4), 143-145.
61. Nicolakakis, N.; Aboulkassim, T.; Ongali, B.; Lecrux, C.; Fernandes, P.; Rosa-Neto, P.; Tong, X.K.; Hamel, E. Complete rescue of cerebrovascular function in aged Alzheimer's disease transgenic mice by antioxidants and pioglitazone, a peroxisome proliferator-activated receptor gamma agonist. J. Neurosci., 2008, 28(37), 9287-9296.
62. Aliev, G.; Castellani, R.J.; Petersen, R.B.; Burnstock, G.; Perry, G.; Smith, M.A. Pathobiology of familial hypercholesterolemicatherosclerosis. J. Submicrosc. Cytol. Pathol., 2004, 36(3-4), 225-240.
63. 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. J. Cell. Molec. Med., 2009, 13(2), 320-333.
64. Matz, R.L.; Schott, C.; Stoclet, J.C.; Andriantsitohaina, R. Agerelated endothelial dysfunction with respect to nitric oxide, endothelium-derived hyperpolarizing factor and cyclooxygenase products. Physiol. Res., 2000, 49(1), 11-18.
65. 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(6), 906-913.
66. 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 Lipoic acid treatment in ApoE4 mouse as a model of human Alzheimer's disease. J. Neurol. Sci., 2009, 283(1-2), 199-206.
67. Aliev, G.; Shi, J.; Perry, G.; Lamb, B.T.; La Manna, J.C.; Friedland, R.P. Neuronal mitochondrial abnormalities in yeast artificial chromosome(YAC) transgenic mice overexpressing amyloid precursor protein(APP). Soc. Neurosci. Abstr. Book, 2000, 30(26).
68. Price, J.M.; Sutton, E.T.; Hellermann, A.; Thomas, T. beta-Amyloid induces cerebrovascular endothelial dysfunction in the rat brain. Neurol. Res., 1997, 19(5), 534-538.
69. Aliev, G.; Liu, J.; Fischbach, K.; Pacheco, G.J.; Palacios, H.; Walrafen, B.; Obrenovich, M.E.; Gasimov, E.; Solis Herrera, A.; Ames, B.N. Feeding acetyl-L-carnitine and lipoic acid to aged rats ameliorates neuronal mitochondria damage. In: The Role of oxidative stress, mitochondria failure and cellular hypoperfusion in the pathobiology of Alzheimer disease. Aliev, G., Ed.; Research Signpost Publisher, 2011, Chapter 13, pp. 273-296.
70. Cash, A.D.; Aliev, G.; Siedlak, S.L.; Fujioka, H.; Vinters, H.V.; Tabaton, M.; Johnson, A.B.; Paula-Barbosa, M.; Avila, J.; Jones, P.K.; Smith, M.A.; Perry, G. Microtubule reduction In Alzheimer disease and aging is independent of filament formation. Am. J. Pathol., 2002, 162(5), 1623-1627.
71. 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(9), 3017-3023.
72. 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(13), 1395-1406.
73. Ames, B.N. Delaying the mitochondrial decay of aging. Ann. NY Acad. Sci., 2004a, 1019, 406-411.
74. Ames, B.N. Mitochondrial decay, a major cause of aging, can be delayed. J. Alzheimers Dis., 2004, 6(2), 117-121.
75. Ames, B.N.; Liu, J. Delaying the mitochondrial decay of aging with acetylcarnitine. Ann. NY Acad. Sci., 2004, 1033, 108-116.
76. 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 Ralpha-lipoic acid. Proc. Natl. Acad. Sci. USA, 2002, 99(4), 2356-2361.
77. 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. NY Acad. Sci., 2004, 1033, 117-131.
78. 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(13), 3756-3762.
79. Gomez-Pinilla, F. Brain foods: the effects of nutrients on brain function. Nat. Rev. Neurosci., 2008, 9(7), 568-578.
80. 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(4), 1876-1881.
81. 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(4), 755-763.
82. Liu, J.; Atamna, H.; Kuratsune, H.; Ames, B.N. Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites. Ann. NY Acad. Sci., 2002, 959, 133-166.
83. Reid, P.C.; Urano, Y.; Kodama, T.; Hamakubo, T. Alzheimer's disease: cholesterol, membrane rafts, isoprenoids and statins. J. Cell. Molec. Med., 2007, 11(3), 383-392.
84. 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(3), 721-730.
85. 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(9), 590-591.
86. Cedazo-Minguez, A. Apolipoprotein E and Alzheimer's disease: molecular mechanisms and therapeutic opportunities. J. Cell. Mol. Med., 2007, 11(6), 1227-1238.
87. 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(3), 198-204.
88. 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(11), 1311-1318.
89. 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(15), 5644-5651.
90. 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(6), 3334-3339.
91. Aliev, G.; Liu, J.; Fischbach, K.; Xu, K;, Puchowicz, M.; Obrenovich, M.E.; Gasimov, E.; Solis Herrera, A.; Ames, B.N.; LaManna, J.C. The response to Lipoic acid and acetyl-L-carnitine regiments in ApoE4 mice serves a model for Alzheimer disease in humans. In: The Role of oxidative stress, mitochondria failure and cellular hypoperfusion in the pathobiology of Alzheimer disease. Aliev, G., Ed.; Research Signpost Publisher, 2011, Chapter 14, pp. 297-316.
92. 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(5-6), 649-663.
93. 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 Azheimer disease. Neurotox. Res., 2003, 5(7), 491-504.
94. 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.