Heme binding to Amyloid-β peptide: Mechanistic role in Alzheimer's disease

Journal of Alzheimer's Disease

Volumn 10, Issue 2-3, 2006, Pages 255-266

  Atamna, Hani ^a  

^a CHILDREN S HOSPITAL OAKLAND RESEARCH INSTITUTE   (United States)

Author keywords

Alzheimer; Amyloid ; A heme; Cholesterol; Copper; Heme; Iron; Metabolism; Mitochondria; Toxic metals; Zinc

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; CHELATING AGENT; HEME; IRON; PEROXIDASE;

ALZHEIMER DISEASE; CHOLESTEROL METABOLISM; CHOLESTEROL SYNTHESIS; CYTOPATHOGENIC EFFECT; DISORDERS OF MITOCHONDRIAL FUNCTIONS; HOMEOSTASIS; HUMAN; IRON METABOLISM; METABOLIC REGULATION; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN BINDING; PROTEIN DEFICIENCY; PROTEIN METABOLISM; PROTEIN PROTEIN INTERACTION; REVIEW; SYNTHESIS;

EID: 33751103136     PISSN: 13872877     EISSN: None     Source Type: Journal    
DOI: 10.3233/JAD-2006-102-310     Document Type: Review

References (114)

1. A. Alzheimer, R.A. Stelzmann, H.N. Schnitzlein and F.R. Murtagh, An English translation of Alzheimer's 1907 paper, "Uber eine eigenartige Erkankung der Hirnrinde", Clin Anat 8 (1995), 429-431.
2. B.N. Ames, Delaying the mitochondrial decay of aging, Ann N Y Acad Sci 1019 (2004), 406-411.
3. H. Atamna, Heme, iron, and the mitochondrial decay of ageing, Ageing Res Rev 3 (2004), 303-318.
4. H. Atamna and W.H. 2nd Frey, A role for heme in Alzheimer's disease: heme binds amyloid beta and has altered metabolism, Proc Natl Acad Sci USA 101 (2004), 11153-11158.
5. H. Atamna and K. Boyle, Amyloid-beta peptide binds with heme to form a peroxidase: Relationship to the cytopathologies of Alzheimer's disease, Proc Natl Acad Sci USA 103 (2006), 3381-3386.
6. H. Atamna, J. Liu and B.N. Ames, Heme deficiency selectively interrupts assembly of mitochondrial complex IV in human fibroblasts: relevance to aging, J Biol Chem 276 (2001), 48410-48416.
7. H. Atamna, P.B. Walter and B.N. Ames, The role of heme and iron-sulfur clusters in mitochondrial biogenesis, maintenance, and decay with age, Arch Biochem Biophys 397 (2002), 345-353.
8. H. Atamna, D.W. Killilea, A.N. Killilea and B.N. Ames, Heme deficiency may be a factor in the mitochondrial and neuronal decay of aging, Proc Natl Acad Sci USA 99 (2002), 14807-14812.
9. S. Baldus, T. Heitzer, J.P. Eiserich, D. Lau, H. Mollnau, M. Ortak, S. Petri, B. Goldmann, H.J. Duchstein, J. Berger, U. Helmchen, B.A. Freeman, T. Meinertz and T. Munzel, Myeloperoxidase enhances nitric oxide catabolism during myocardial ischemia and reperfusion, Free Radic Biol Med 37 (2004), 902-911.
10. M.F. Beal, Energetics in the pathogenesis of neurodegenerative diseases, Trends Neurosci 23 (2000), 298-304.
11. L.M. Billings, S. Oddo, K.N. Green, J.L. McGaugh and F.M. Laferla, Intraneuronal Abeta causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice, Neuron 45 (2005), 675-688.
12. J.P. Blass, Brain metabolism and brain disease: is metabolic deficiency the proximate cause of Alzheimer dementia? J Neurosci Res 66 (2001), 851-856.
13. V.W. Bloks, T. Plosch, H. van Goor, H. Roelofsen, J. Baller, R. Havinga, H.J. Verkade, A. van Tol, P.L. Jansen and F. Kuipers, Hyperlipidemia and atherosclerosis associated with liver disease in ferrochelatase-deficient mice, J Lipid Res 42 (2001), 41-50.
14. E. Bossy-Wetzel, R. Schwarzenbacher and S.A. Lipton, Molecular pathways to neurodegeneration, Nat Med 10 Suppl (2004), S2-9.
15. R. Brookmeyer, S. Gray and C. Kawas, Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset, Am J Public Health 88 (1998), 1337-1342.
16. A.I. Bush, The metallobiology of Alzheimer's disease, Trends Neurosci 26 (2003), 207-214.
17. E. Cadenas and K.J. Davies, Mitochondrial free radical generation, oxidative stress, and aging, Free Radic Biol Med 29 (2000), 222-230.
18. A. Campbell, The potential role of aluminium in Alzheimer's disease, Nephrol Dial Transplant 17 Suppl 2 (2002), 17-20.
19. L. Canevari, A.Y. Abramov and M.R. Duchen, Toxicity of amyloid beta peptide: tales of calcium, mitochondria, and oxidative stress, Neurochem Res 29 (2004), 637-650.
20. L.M. Canzoniero, D.M. Turetsky and D.W. Choi, Measurement of intracellular free zinc concentrations accompanying zinc-induced neuronal death, J Neurosci 19 (1999), RC31(31-36).
21. Y. Chen, W. Liu, L. Naumovski and R.L. Neve, ASPP2 inhibits APP-BP1-mediated NEDD8 conjugation to cullin-1 and decreases APP-BP1-induced cell proliferation and neuronal apoptosis, J Neurochem 85 (2003), 801-809.
22. T. Chernova, P. Nicotera and A.G. Smith, Heme deficiency is associated with senescence and causes suppression of N-methyl-D-aspartate receptor subunits expression in primary cortical neurons, Mol Pharmacol 69 (2006), 697-705.
23. J.R. Connor, S.L. Menzies, S.M. St Martin and E.J. Mufson, A histochemical study of iron, transferrin, and ferritin in Alzheimer's diseased brains, J Neurosci Res 31 (1992), 75-83.
24. J.R. Connor, B.S. Snyder, J.L. Beard, R.E. Fine and E.J. Mufson, Regional distribution of iron and iron-regulatory proteins in the brain in aging and Alzheimer's disease, J Neurosci Res 31 (1992), 327-335.
25. W.E. Daniell, H.L. Stockbridge, R.F. Labbe, J.S. Woods, K.E. Anderson, D.M. Bissell, J.R. Bloomer, R.D. Ellefson, M.R. Moore, C.A. Pierach, W.E. Schreiber, A. Tefferi and G.M. Franklin. Environmental chemical exposures and disturbances of heme synthesis, Environ Health Perspect 105 Suppl 1 (1997), 37-53.
26. S. Dhakshinamoorthy, A.K. Jain, D.A. Bloom and A.K. Jaiswal, Bach1 Competes with Nrf2 Leading to Negative Regulation of the Antioxidant Response Element (ARE)-mediated NAD(P)H:Quinone Oxidoreductase 1 Gene Expression and Induction in Response to Antioxidants, J Biol Chem 280 (2005), 16891-16900.
27. E.M. Dioum, J. Rutter, J.R. Tuckerman, G. Gonzalez, M.A. Gilles-Gonzalez and S.L. McKnight, NPAS2: a gas-responsive transcription factor, Science 298 (2002), 2385-2387.
28. R. Distl, V. Meske and T.G. Ohm, Tangle-bearing neurons contain more free cholesterol than adjacent tangle-free neurons, Acta Neuropathol (Berl) 101 (2001), 547-554.
29. H.B. Dunford and Y. Hsuanyu, Kinetics of oxidation of serotonin by myeloperoxidase compounds I and II, Biochem Cell Biol 77 (1999), 449-457.
30. B.E. Dwyer, A. Takeda, X. Zhu, G. Perry and M.A. Smith, Ferric cycle activity and Alzheimer disease, Curr Neurovasc Res 2 (2005), 261-267.
31. J.R. Fawcett, E.Z. Bordayo, K. Jackson, H. Liu, J. Peterson, A. Svitak and W.H. 2nd Frey, Inactivation of the human brain muscarinic acetylcholine receptor by oxidative damage catalyzed by a low molecular weight endogenous inhibitor from Alzheimer's brain is prevented by pyrophosphate analogs, bioflavonoids and other antioxidants, Brain Res 950 (2002), 10-20.
32. R. Fukuyama, T. Mizuno, S. Mori, K. Nakajima, S. Fushiki and K. Yanagisawa, Age-dependent change in the levels of Abeta40 and Abeta42 in cerebrospinal fluid from control subjects, and a decrease in the ratio of Abeta42 to Abeta40 level in cerebrospinal fluid from Alzheimer's disease patients, Eur Neurol 43 (2000), 155-160.
33. C. Giulivi, A. Boveris and E. Cadenas, Hydroxyl radical generation during mitochondrial electron transfer and the formation of 8-hydroxydesoxyguanosine in mitochondrial DNA, Arch Biochem Biophys 316 (1995), 909-916.
34. C. Glabe, Intracellular mechanisms of amyloid accumulation and pathogenesis in Alzheimer's disease, J Mol Neurosci 17 (2001), 137-145.
35. L.S. Goessling, D.P. Mascotti and R.E. Thach, Involvement of heme in the degradation of iron-regulatory protein 2, J Biol Chem 273 (1998), 12555-12557.
36. T.E. Golde and C. Janus, Homing in on intracellular Abeta? Neuron 45 (2005), 639-642.
37. L. Gouya, C. Martin-Schmitt, A.M. Robreau, F. Austerlitz, V.D. Silva, P. Brun, S. Simonin, S. Lyoumi, B. Grandchamp, C. Beaumont, H. Puy and J.C. Deybach, Contribution of a common single-nucleotide polymorphism to the genetic predisposition for erythropoietic protoporphyria, Am J Hum Genet 78 (2006), 2-14.
38. S. Granick and S. Sassa, d-aminolevulinic acid synthetase and the control of heme and chlorophyll synthesis, 3rd ed., New York and London: Academic Press, 1971.
39. G.F. Grinstead, J.M. Trzaskos, J.T. Billheimer and J.L. Gaylor, Cytosolic modulators of activities of microsomal enzymes of cholesterol biosynthesis. Effects of Acyl-CoA inhibition and cytosolic Z-protein, Biochim Biophys Acta 751 (1983), 41-51.
40. T. Hon, A. Hach, H.C. Lee, T. Cheng and L. Zhang, Functional analysis of heme regulatory elements of the transcriptional activator Hap1, Biochem Biophys Res Commun 273 (2000), 584-591.
41. D. Howlett, P. Cutler, S. Heales and P. Camilleri, Hemin and related porphyrins inhibit beta-amyloid aggregation, FEBS Lett 417 (1997), 249-251.
42. L.J. Ignarro, B. Ballot and K.S. Wood, Regulation of soluble guanylate cyclase activity by porphyrins and metalloporphyrins, J Biol Chem 259 (1984), 6201-6207.
43. I. Isobe, M. Michikawa and K. Yanagisawa, Enhancement of MTT, a tetrazolium salt, exocytosis by amyloid beta-protein and chloroquine in cultured rat astrocytes, Neurosci Lett 266 (1999), 129-132.
44. P. Juzenas, A. Juzeniene, O. Kaalhus, V. Iani and J. Moan, Noninvasive fluorescence excitation spectroscopy during application of 5-aminolevulinic acid in vivo, Photochem Photobiol Sci 1 (2002), 745-748.
45. F. Kamenetz, T. Tomita, H. Hsieh, G. Seabrook, D. Borchelt, T. Iwatsubo, S. Sisodia and R. Malinow, APP processing and synaptic function, Neuron 37 (2003), 925-937.
46. U. Keil, A. Bonert, C.A. Marques, I. Scherping, J. Weyermann, J.B. Strosznajder, F. Muller-Spahn, C. Haass, C. Czech, L. Pradier, W.E. Muller and A. Eckert, Amyloid beta-induced changes in nitric oxide production and mitochondrial activity lead to apoptosis, J Biol Chem 279 (2004), 50310-50320.
47. S.N. Kelada, E. Shelton, R.B. Kaufmann and M.J. Khoury, Delta-aminolevulinic acid dehydratase genotype and lead toxicity: a HuGE review, Am J Epidemiol 154 (2001), 1-13.
48. M.A. Kennedy, R. Barbuch and M. Bard, Transcriptional regulation of the squalene synthase gene (ERG9) in the yeast Saccharomyces cerevisiae, Biochim Biophys Acta 1445 (1999), 110-122.
49. T. Kimpara, A. Takeda, T. Yamaguchi, H. Arai, N. Okita, S. Takase, H. Sasaki and Y. Itoyama, Increased bilirubins and their derivatives in cerebrospinal fluid in Alzheimer's disease, Neurobiol Aging 21 (2000), 551-554.
50. A.M. Konijn, H. Glickstein, B. Vaisman, E.G. Meyron-Holtz, I.N. Slotki and Z.I. Cabantchik, The cellular labile iron pool and intracellular ferritin in K562 cells, Blood 94 (1999), 2128-2134.
51. J.T. Lathrop and M.P. Timko, Regulation by heme of mitochondrial protein transport through a conserved amino acid motif, Science 259 (1993), 522-525.
52. M.A. Leissring, W. Farris, A.Y. Chang, D.M. Walsh, X. Wu, X. Sun, M.P. Frosch and D.J. Selkoe, Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death, Neuron 40 (2003), 1087-1093.
53. D.A. Litman and M.A. Correia, Elevated brain tryptophan and enhanced 5-hydroxytryptamine turnover in acute hepatic heme deficiency: clinical implications, J Pharmacol Exp Ther 232 (1985), 337-345.
54. Y. Liu, Understanding the biological activity of amyloid proteins in vitro: from inhibited cellular MTT reduction to altered cellular cholesterol homeostatis, Prog Neuropsychopharmacol Biol Psychiatry 23 (1999), 377-395.
55. Y. Liu, D.A. Peterson and D. Schubert, Amyloid beta peptide alters intracellular vesicle trafficking and cholesterol homeostasis, Proc Natl Acad Sci USA 95 (1998), 13266-13271.
56. J.W. Lustbader, M. Cirilli, C. Lin, H.W. Xu, K. Takuma, N. Wang, C. Caspersen, X. Chen, S. Pollak, M. Chaney, F. Trinchese, S. Liu, F. Gunn-Moore, L.F. Lue, D.G. Walker, P. Kuppusamy, Z.L. Zewier, O. Arancio, D. Stern, S.S. Yan and H. Wu, ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease, Science 304 (2004), 448-452.
57. M. Manczak, T.S. Anekonda, E. Henson, B.S. Park, J. Quinn and P.H. Reddy, Mitochondria are a direct site of Abeta accumulation in Alzheimer's disease neurons: implications for free radical generation and oxidative damage in disease progression, Hum Mol Genet 15 (2006), 1437-1449.
58. M.P. Mattson, Pathways towards and away from Alzheimer's disease, Nature 430 (2004), 631-639.
59. W.K. Jr. McCoubrey, T.J. Huang and M.D. Maines, Heme oxygenase-2 is a hemoprotein and binds heme through heme regulatory motifs that are not involved in heme catalysis, J Biol Chem 272 (1997), 12568-12574.
60. L.J. Miller and R. Chacko, The role of cholesterol and statins in Alzheimer's disease, Ann Pharmacother 38 (2004), 91-98.
61. G. Minopoli, P. de Candia, A. Bonetti, R. Faraonio, N. Zambrano and T. Russo, The beta-amyloid precursor protein functions as a cytosolic anchoring site that prevents Fe65 nuclear translocation, J Biol Chem 276 (2001), 6545-6550.
62. A.C. Miu, A.I. Olteanu and M. Miclea, A behavioral and ultrastructural dissection of the interference of aluminum with aging, J Alzheimers Dis 6 (2004), 315-328.
63. T. Mori, D. Paris, T. Town, A.M. Rojiani, D.L. Sparks, A. Delledonne, F. Crawford, L.I. Abdullah, J.A. Humphrey, D.W. Dickson and M.J. Mullan, Cholesterol accumulates in senile plaques of Alzheimer disease patients and in transgenic APP(SW) mice, J Neuropathol Exp Neurol 60 (2001), 778-785.
64. S.D. Morris, N.G. Mason, G.H. Elder, J.L. Hawk and R.P. Sarkany, Ferrochelatase gene polymorphism analysis for accurate genetic counselling in erythropoietic protoporphyria, Br J Dermatol 147 (2002), 572-574.
65. L. Mucke, E. Masliah, G.Q. Yu, M. Mallory, E.M. Rockenstein, G. Tatsuno, K. Hu, D. Kholodenko, K. Johnson-Wood and L. McConlogue, High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation, J Neurosci 20 (2000), 4050-4058.
66. E.M. Mutisya, A.C. Bowling and M.F. Beal, Cortical cytochrome oxidase activity is reduced in Alzheimer's disease, J Neurochem 63 (1994), 2179-2184.
67. E. Napoli, F. Taroni and G.A. Cortopassi, Frataxin, Iron-Sulfur Clusters, Heme, ROS, and Aging, Antioxid Redox Signal 8 (2006), 506-516.
68. K. Ogawa, J. Sun, S. Taketani, O. Nakajima, C. Nishitani, S. Sassa, N. Hayashi, M. Yamamoto, S. Shibahara, H. Fujita and K. Igarashi, Heme mediates derepression of Maf recognition element through direct binding to transcription repressor Bach1, Embo J 20 (2001), 2835-2843.
69. Y. Ohyagi, H. Asahara, D.H. Chui, Y. Tsuruta, N. Sakae, K. Miyoshi, T. Yamada, H. Kikuchi, T. Taniwaki, H. Murai, K. Ikezoe, H. Furuya, T. Kawarabayashi, M. Shoji, F. Checler, T. Iwaki, T. Makifuchi, K. Takeda, J. Kira and T. Tabira, Intracellular Abeta42 activates p53 promoter: a pathway to neurodegeneration in Alzheimer's disease, Faseb J 19 (2005), 255-257.
70. M.A. Pappolla, Y.J. Chyan, R.A. Omar, K. Hsiao, G. Perry, M.A. Smith and P. Bozner, Evidence of oxidative stress and in vivo neurotoxicity of beta-amyloid in a transgenic mouse model of Alzheimer's disease: a chronic oxidative paradigm for testing antioxidant therapies in vivo, Am J Pathol 152 (1998), 871-877.
71. W.D. Jr. Parker, J. Parks, C.M. Filley and B.K. Kleinschmidt-DeMasters, Electron transport chain defects in Alzheimer's disease brain, Neurology 44 (1994), 1090-1096.
72. C. Perotti, H. Fukuda, G. DiVenosa, A.J. MacRobert, A. Batlle and A. Casas, Porphyrin synthesis from ALA derivatives for photodynamic therapy. In vitro and in vivo studies, Br J Cancer 90 (2004), 1660-1665.
73. J.L. Perrot, C. Guy, G. Bour Guichenez, O. Amigues, J. Servoz and F. Cambazard, Porphyria cutanea tarda induced by HMG CoA reductase inhibitors: simvastatin, pravastatin, Ann Dermatol Venereol 121 (1994), 817-819.
74. I.B. Pinnix, G.S. Guzman, H.L. Bonkovsky, S.R. Zaki and J.M. Jr. Kinkade, The post-translational processing of myeloperoxidase is regulated by the availability of heme, Arch Biochem Biophys 312 (1994), 447-458.
75. L.D. Plant, J.P. Boyle, I.F. Smith, C. Peers and H.A. Pearson, The production of amyloid beta peptide is a critical requirement for the viability of central neurons, J Neurosci 23 (2003), 5531-5535.
76. P. Ponka, J. Borova and J. Neuwirt, Accumulation of heme in mitochondria from rabbit reticulocytes with inhibited globin synthesis, Biochim Biophys Acta 304 (1973), 715-718.
77. W.Q. Qiu, A. Ferreira, C. Miller, E.H. Koo and D.J. Selkoe, Cell-surface beta-amyloid precursor protein stimulates neurite outgrowth of hippocampal neurons in an isoform-dependent manner, J Neurosci 15 (1995), 2157-2167.
78. T.D. Rae, P.J. Schmidt, R.A. Pufahl, V.C. Culotta and T.V. O'Halloran, Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase, Science 284 (1999), 805-808.
79. T. Ramasarma and S. Usha Devi. Mechanism of inactivation of HMGCoA reductase, Indian J Biochem Biophys 24 (1987), suppl 33-35.
80. S. Sassa, Why heme needs to be degraded to iron, biliverdin IXalpha, and carbon monoxide? Antioxid Redox Signal 6 (2004), 819-824.
81. J. Saxton, O.L. Lopez, G. Ratcliff, C. Dulberg, L.P. Fried, M.C. Carlson, A.B. Newman and L. Kuller, Preclinical Alzheimer disease: neuropsychological test performance 1.5 to 8 years prior to onset, Neurology 63 (2004), 2341-2347.
82. A. Schindl, F. Trautinger, H. Pernerstorfer-Schon, C. Konnaris and H. Honigsmann, Porphyria cutanea tarda induced by the use of pravastatin, Arch Dermatol 134 (1998), 1305-1306.
83. H.M. Schipper, S. Cisse and E.G. Stopa, Expression of heme oxygenase-1 in the senescent and Alzheimer-diseased brain, Ann Neurol 37 (1995), 758-768.
84. N. Schoenfeld, R. Mamet, Y. Lurie, P. Green, Y. Bomstein and A. Atsmon, The porphyrinogenic effect of simvastatin in experimental systems, Biomed Pharmacother 43 (1989), 135-139.
85. R.A. Schoenfeld, E. Napoli, A. Wong, S. Zhan, L. Reutenauer, D. Morin, A.R. Buckpitt, F. Taroni, B. Lonnerdal, M. Ristow, H. Puccio and G.A. Cortopassi, Frataxin deficiency alters heme pathway transcripts and decreases mitochondrial heme metabolites in mammalian cells, Hum Mol Genet (2005).
86. D.J. Selkoe, Toward a comprehensive theory for Alzheimer's disease. Hypothesis: Alzheimer's disease is caused by the cerebral accumulation and cytotoxicity of amyloid beta-protein, Ann N Y Acad Sci 924 (2000), 17-25.
87. D.J. Selkoe, Alzheimer's disease: genes, proteins, and therapy, Physiol Rev 81 (2001), 741-766.
88. D.J. Selkoe, Clearing the brain's amyloid cobwebs, Neuron 32 (2001), 177-180.
89. D.J. Selkoe, Alzheimer's disease is a synaptic failure, Science 298 (2002), 789-791.
90. N. Shinjyo and K. Kita, Up-Regulation of Heme Biosynthesis during Differentiation of Neuro2a Cells, J Biochem (Tokyo) 139 (2006), 373-381.
91. D.M. Skovronsky, R.W. Doms and V.M. Lee, Detection of a novel intraneuronal pool of insoluble amyloid beta protein that accumulates with time in culture, J Cell Biol 141 (1998), 1031-1039.
92. A. Smith, Homeostasis of heme in health and disease: current aspects of the structural biology of heme-protein interactions and of gene regulation, DNA Cell Biol 21 (2002), 245-249.
93. M.A. Smith, K. Wehr, P.L. Harris, S.L. Siedlak, J.R. Connor and G. Perry, Abnormal localization of iron regulatory protein in Alzheimer's disease, Brain Res 788 (1998), 232-236.
94. M.A. Smith, R.K. Kutty, P.L. Richey, S.D. Yan, D. Stern, G.J. Chader, B. Wiggert, R.B. Petersen and G. Perry, Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer's disease, Am J Pathol 145 (1994), 42-47.
95. R.S. Sohal, Aging, cytochrome oxidase activity, and hydrogen peroxide release by mitochondria, Free Radic Biol Med 14 (1993), 583-588.
96. Y. Sun, K. Jin, A. Peel, X.O. Mao, L. Xie and D.A. Greenberg, Neuroglobin protects the brain from experimental stroke in vivo, Proc Natl Acad Sci USA 100 (2003), 3497-3500.
97. H. Suzuki, S. Tashiro, S. Hira, J. Sun, C. Yamazaki, Y. Zenke, M. Ikeda-Saito, M. Yoshida and K. Igarashi, Heme regulates gene expression by triggering Crm1-dependent nuclear export of Bach1, Embo J 23 (2004), 2544-2553.
98. M. Takahashi, S. Dore, C.D. Ferris, T. Tomita, A. Sawa, H. Wolosker, D.R. Borchelt, T. Iwatsubo, S.H. Kim, G. Thinakaran, S.S. Sisodia and S.H. Snyder, Amyloid precursor proteins inhibit heme oxygenase activity and augment neurotoxicity in Alzheimer's disease, Neuron 28 (2000), 461-473.
99. R.H. Takahashi, C.G. Almeida, P.F. Kearney, F. Yu, M.T. Lin, T.A. Milner and G.K. Gouras, Oligomerization of Alzheimer's beta-amyloid within processes and synapses of cultured neurons and brain, J Neurosci 24 (2004), 3592-3599.
100. P.R. Turner, K. O'Connor, W.P. Tate and W.C. Abraham, Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory, Prog Neurobiol 70 (2003), 1-32.
101. S. Usha Devi and T. Ramasarma, Hemin-mediated oxidative inactivation of 3-hydroxy-3-methylglutaryl CoA reductase, Mol Cell Biochem 77 (1987), 103-110.
102. J. Valla, J.D. Berndt and F. Gonzalez-Lima, Energy hypometabolism in posterior cingulate cortex of Alzheimer's patients: superficial laminar cytochrome oxidase associated with disease duration, J Neurosci 21 (2001), 4923-4930.
103. H.D. Jr. Venters, L.E. Bonilla, T. Jensen, H.P. Garner, E.Z. Bordayo, M.M. Najarian, T.A. Ala, R.P. Mason and W.H. 2nd Frey, Heme from Alzheimer's brain inhibits muscarinic receptor binding via thiyl radical generation, Brain Res 764 (1997), 93-100.
104. K.R. Wagner, F.R. Sharp, T.D. Ardizzone, A. Lu and J.F. Clark, Heme and iron metabolism: role in cerebral hemorrhage, J Cereb Blood Flow Metab 23 (2003), 629-652.
105. D.M. Walsh, B.P. Tseng, R.E. Rydel, M.B. Podlisny and D.J. Selkoe, The oligomerization of amyloid beta-protein begins intracellularly in cells derived from human brain, Biochemistry 39 (2000), 10831-10839.
106. A. Wielburski and B.D. Nelson, Heme-a induces assembly of rat liver cytochrome c oxidase subunits I-III in isolated mitochondria, FEBS Lett 177 (1984), 291-294.
107. B. Wolozin, J. 3rd Brown, C. Theisler and S. Silberman, The cellular biochemistry of cholesterol and statins: insights into the pathophysiology and therapy of Alzheimer's disease, CNS Drug Rev 10 (2004), 127-146.
108. S.D. Yan and D.M. Stern, Mitochondrial dysfunction and Alzheimer's disease: role of amyloid-beta peptide alcohol dehydrogenase (ABAD), Int J Exp Pathol 86 (2005), 161-171.
109. P.J. Yao, Synaptic frailty and clathrin-mediated synaptic vesicle trafficking in Alzheimer's disease, Trends Neurosci 27 (2004), 24-29.
110. W. Ye and L. Zhang, Heme controls the expression of cell cycle regulators and cell growth in HeLa cells, Biochem Biophys Res Commun 315 (2004), 546-554.
111. R.A. Yokel, The toxicology of aluminum in the brain: a review, Neurotoxicology 21 (2000), 813-828.
112. L. Zhang and L. Guarente, Heme binds to a short sequence that serves a regulatory function in diverse proteins, Embo J 14 (1995), 313-320.
113. Y. Zhu, T. Hon, W. Ye and L. Zhang, Heme deficiency interferes with the Ras-mitogen-activated protein kinase signaling pathway and expression of a subset of neuronal genes, Cell Growth Differ 13 (2002), 431-439.
114. Y. Zhu, Y. Sun, K. Jin and D.A. Greenberg, Hemin induces neuroglobin expression in neural cells, Blood 100 (2002), 2494-2498.