The Role of Hypoxia-Inducible Factor 1 in Mild Cognitive Impairment

Abstract

Neuroinflammation and reactive oxygen species are thought to mediate the pathogenesis of Alzheimer’s disease (AD), suggesting that mild cognitive impairment (MCI), a prodromal stage of AD, may be driven by similar insults. Several studies document that hypoxia-inducible factor 1 (HIF-1) is neuroprotective in the setting of neuronal insults, since this transcription factor drives the expression of critical genes that diminish neuronal cell death. HIF-1 facilitates glycolysis and glucose metabolism, thus helping to generate reductive equivalents of NADH/NADPH that counter oxidative stress. HIF-1 also improves cerebral blood flow which opposes the toxicity of hypoxia. Increased HIF-1 activity and/or expression of HIF-1 target genes, such as those involved in glycolysis or vascular flow, may be an early adaptation to the oxidative stressors that characterize MCI pathology. The molecular events that constitute this early adaptation are likely neuroprotective, and might mitigate cognitive decline or the onset of full-blown AD. On the other hand, prolonged or overwhelming stressors can convert HIF-1 into an activator of cell death through agents such as Bnip3, an event that is more likely to occur in late MCI or advanced Alzheimer’s dementia.

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References

  1. Adamcio B, Sargin D, Stradomska A, Medrihan L, Gertler C, Theis F, Zhang M, Muller M, Hassouna I, Hannke K et al (2008) Erythropoietin enhances hippocampal long-term potentiation and memory. BMC Biol 6:37

    Article  PubMed  PubMed Central  Google Scholar 

  2. Adamcio B, Sperling S, Hagemeyer N, Walkinshaw G, Ehrenreich H (2010) Hypoxia inducible factor stabilization leads to lasting improvement of hippocampal memory in healthy mice. Behav Brain Res 208:80–84

    CAS  Article  PubMed  Google Scholar 

  3. Alonso A, de Larriva APA (2016) Atrial fibrillation, cognitive decline and dementia. Eur Cardiol 11:49–53

    Article  PubMed  PubMed Central  Google Scholar 

  4. Althaus J, Bernaudin M, Petit E, Toutain J, Touzani O, Rami A (2006) Expression of the gene encoding the pro-apoptotic BNIP3 protein and stimulation of hypoxia-inducible factor-1alpha (HIF-1alpha) protein following focal cerebral ischemia in rats. Neurochem Int 48:687–695

    CAS  Article  PubMed  Google Scholar 

  5. Barja G (2004) Free radicals and aging. Trends Neurosci 27:595–600

    CAS  Article  PubMed  Google Scholar 

  6. Bell RD, Winkler EA, Singh I, Sagare AP, Deane R, Wu Z, Holtzman DM, Betsholtz C, Armulik A, Sallstrom J et al (2012) Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature 485:512–516

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. Brand K (1997) Aerobic glycolysis by proliferating cells: protection against oxidative stress at the expense of energy yield. J Bioenerg Biomembr 29:355–364

    CAS  Article  PubMed  Google Scholar 

  8. Brodie FG, Panerai RB, Foster S, Evans DH, Robinson TG (2009) Long-term changes in dynamic cerebral autoregulation: a 10 years follow up study. Clin Physiol Funct Imaging 29:366–371

    Article  PubMed  Google Scholar 

  9. Bruick RK (2000) Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc Natl Acad Sci USA 97:9082–9087

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. Butterfield DA, Poon HF, St Clair D, Keller JN, Pierce WM, Klein JB, Markesbery WR (2006) Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: insights into the development of Alzheimer’s disease. Neurobiol Dis 22:223–232

    CAS  Article  PubMed  Google Scholar 

  11. Cao L, Jiao X, Zuzga DS, Liu Y, Fong DM, Young D, During MJ (2004) VEGF links hippocampal activity with neurogenesis, learning and memory. Nat Genet 36:827–835

    CAS  Article  PubMed  Google Scholar 

  12. Chen C, Pore N, Behrooz A, Ismail-Beigi F, Maity A (2001) Regulation of glut1 mRNA by hypoxia-inducible factor-1. Interaction between H-ras and hypoxia. J Biol Chem 276:9519–9525

    CAS  Article  PubMed  Google Scholar 

  13. Corder EH, Ervin JF, Lockhart E, Szymanski MH, Schmechel DE, Hulette CM (2005) Cardiovascular damage in Alzheimer disease: autopsy findings from the Bryan ADRC. J Biomed Biotechnol 2005:189–197

    Article  PubMed  PubMed Central  Google Scholar 

  14. Cosentino-Gomes D, Rocco-Machado N, Meyer-Fernandes JR (2012) Cell signaling through protein kinase C oxidation and activation. Int J Mol Sci 13:10697–10721

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Daulatzai MA (2016) Cerebral hypoperfusion and glucose hypometabolism: key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer’s disease. J Neurosci Res. doi:10.1002/jnr.23777

    PubMed  Google Scholar 

  16. Davies TA, Long HJ, Sgro K, Rathbun WH, McMenamin ME, Seetoo K, Tibbles H, Billingslea AM, Fine RE, Fishman JB et al (1997) Activated Alzheimer disease platelets retain more beta amyloid precursor protein. Neurobiol Aging 18:147–153

    CAS  Article  PubMed  Google Scholar 

  17. Dehne N, Brune B (2009) HIF-1 in the inflammatory microenvironment. Exp Cell Res 315:1791–1797

    CAS  Article  PubMed  Google Scholar 

  18. Dekker LV, Leitges M, Altschuler G, Mistry N, McDermott A, Roes J, Segal AW (2000) Protein kinase C-beta contributes to NADPH oxidase activation in neutrophils. Biochem J 347(Pt 1):285–289

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. El Benna J, Faust RP, Johnson JL, Babior BM (1996) Phosphorylation of the respiratory burst oxidase subunit p47phox as determined by two-dimensional phosphopeptide mapping. Phosphorylation by protein kinase C, protein kinase A, and a mitogen-activated protein kinase. J Biol Chem 271:6374–6378

    Article  PubMed  Google Scholar 

  20. Farooqui AA, Farooqui T, Panza F, Frisardi V (2012) Metabolic syndrome as a risk factor for neurological disorders. Cell Mol Life Sci 69:741–762

    CAS  Article  PubMed  Google Scholar 

  21. Fillit H, Ding WH, Buee L, Kalman J, Altstiel L, Lawlor B, Wolf-Klein G (1991) Elevated circulating tumor necrosis factor levels in Alzheimer’s disease. Neurosci Lett 129:318–320

    CAS  Article  PubMed  Google Scholar 

  22. Fine JM, Baillargeon AM, Renner DB, Hoerster NS, Tokarev J, Colton S, Pelleg A, Andrews A, Sparley KA, Krogh KM et al (2012) Intranasal deferoxamine improves performance in radial arm water maze, stabilizes HIF-1alpha, and phosphorylates GSK3beta in P301L tau transgenic mice. Exp Brain Res 219:381–390

    CAS  Article  PubMed  Google Scholar 

  23. Flicker C, Ferris SH, Reisberg B (1991) Mild cognitive impairment in the elderly: predictors of dementia. Neurology 41:1006–1009

    CAS  Article  PubMed  Google Scholar 

  24. Fong GH, Takeda K (2008) Role and regulation of prolyl hydroxylase domain proteins. Cell Death Differ 15:635–641

    CAS  Article  PubMed  Google Scholar 

  25. Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL (1996) Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 16:4604–4613

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. Frede S, Stockmann C, Freitag P, Fandrey J (2006) Bacterial lipopolysaccharide induces HIF-1 activation in human monocytes via p44/42 MAPK and NF-kappaB. Biochem J 396:517–527

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. Gao L, Mejias R, Echevarria M, Lopez-Barneo J (2004) Induction of the glucose-6-phosphate dehydrogenase gene expression by chronic hypoxia in PC12 cells. FEBS Lett 569:256–260

    CAS  Article  PubMed  Google Scholar 

  28. Goritz C, Frisen J (2012) Neural stem cells and neurogenesis in the adult. Cell Stem Cell 10:657–659

    Article  PubMed  Google Scholar 

  29. Grammas P, Samany PG, Thirumangalakudi L (2006) Thrombin and inflammatory proteins are elevated in Alzheimer’s disease microvessels: implications for disease pathogenesis. J Alzheimers Dis 9:51–58

    CAS  Article  PubMed  Google Scholar 

  30. Haddad JJ, Land SC (2001) A non-hypoxic, ROS-sensitive pathway mediates TNF-alpha-dependent regulation of HIF-1alpha. FEBS Lett 505:269–274

    CAS  Article  PubMed  Google Scholar 

  31. Halterman MW, Federoff HJ (1999) HIF-1alpha and p53 promote hypoxia-induced delayed neuronal death in models of CNS ischemia. Exp Neurol 159:65–72

    CAS  Article  PubMed  Google Scholar 

  32. Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11:298–300

    CAS  Article  PubMed  Google Scholar 

  33. Hauss-Wegrzyniak B, Dobrzanski P, Stoehr JD, Wenk GL (1998) Chronic neuroinflammation in rats reproduces components of the neurobiology of Alzheimer’s disease. Brain Res 780:294–303

    CAS  Article  PubMed  Google Scholar 

  34. Hellwig-Burgel T, Rutkowski K, Metzen E, Fandrey J, Jelkmann W (1999) Interleukin-1beta and tumor necrosis factor-alpha stimulate DNA binding of hypoxia-inducible factor-1. Blood 94:1561–1567

    CAS  PubMed  Google Scholar 

  35. Hensley K, Carney JM, Mattson MP, Aksenova M, Harris M, Wu JF, Floyd RA, Butterfield DA (1994) A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proc Natl Acad Sci USA 91:3270–3274

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. Hochstenbach J, Mulder T, van Limbeek J, Donders R, Schoonderwaldt H (1998) Cognitive decline following stroke: a comprehensive study of cognitive decline following stroke. J Clin Exp Neuropsychol 20:503–517

    CAS  Article  PubMed  Google Scholar 

  37. Huang HC, Jiang ZF (2009) Accumulated amyloid-beta peptide and hyperphosphorylated tau protein: relationship and links in Alzheimer’s disease. J Alzheimers Dis 16:15–27

    CAS  Article  PubMed  Google Scholar 

  38. Ishii T, Haga S (1975) Identification of components of immunoglobulins in senile plaques by means of fluorescent antibody technique. Acta Neuropathol 32:157–162

    CAS  Article  PubMed  Google Scholar 

  39. Iyalomhe O, Chen Y, Allard J, Ntekim O, Johnson S, Bond V, Goerlitz D, Li J, Obisesan TO (2015) A standardized randomized 6-month aerobic exercise-training down-regulated pro-inflammatory genes, but up-regulated anti-inflammatory, neuron survival and axon growth-related genes. Exp Gerontol 69:159–169

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. Kaur J (2014) A comprehensive review on metabolic syndrome. Cardiol Res Pract 2014:943162

    PubMed  PubMed Central  Google Scholar 

  41. Kim JW, Tchernyshyov I, Semenza GL, Dang CV (2006) HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 3:177–185

    Article  PubMed  Google Scholar 

  42. Li L, Frei B (2006) Iron chelation inhibits NF-kappaB-mediated adhesion molecule expression by inhibiting p22(phox) protein expression and NADPH oxidase activity. Arterioscler Thromb Vasc Biol 26:2638–2643

    CAS  Article  PubMed  Google Scholar 

  43. Li L, Candelario KM, Thomas K, Wang R, Wright K, Messier A, Cunningham LA (2014) Hypoxia inducible factor-1alpha (HIF-1alpha) is required for neural stem cell maintenance and vascular stability in the adult mouse SVZ. J Neurosci Off J Soc Neurosci 34:16713–16719

    Article  Google Scholar 

  44. Marin-Hernandez A, Gallardo-Perez JC, Ralph SJ, Rodriguez-Enriquez S, Moreno-Sanchez R (2009) HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms. Mini Rev Med Chem 9:1084–1101

    CAS  Article  PubMed  Google Scholar 

  45. Markesbery WR (1997) Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med 23:134–147

    CAS  Article  PubMed  Google Scholar 

  46. Masson N, Ratcliffe PJ (2003) HIF prolyl and asparaginyl hydroxylases in the biological response to intracellular O(2) levels. J Cell Sci 116:3041–3049

    CAS  Article  PubMed  Google Scholar 

  47. McCaulley ME, Grush KA (2015) Alzheimer’s disease: exploring the role of inflammation and implications for treatment. Int J Alzheimer’s Dis 2015:515248

    Google Scholar 

  48. McNeill LA, Flashman E, Buck MR, Hewitson KS, Clifton IJ, Jeschke G, Claridge TD, Ehrismann D, Oldham NJ, Schofield CJ (2005) Hypoxia-inducible factor prolyl hydroxylase 2 has a high affinity for ferrous iron and 2-oxoglutarate. Mol Bisyst 1:321–324

    CAS  Article  Google Scholar 

  49. Michiels C, Minet E, Mottet D, Raes M (2002) Regulation of gene expression by oxygen: NF-kappaB and HIF-1, two extremes. Free Radic Biol Med 33:1231–1242

    CAS  Article  PubMed  Google Scholar 

  50. Nagata K, Yamazaki T, Takano D, Maeda T, Fujimaki Y, Nakase T, Sato Y (2016) Cerebral circulation in aging. Ageing Res Rev 30:49–60

    Article  PubMed  Google Scholar 

  51. Nanduri J, Vaddi DR, Khan SA, Wang N, Makarenko V, Semenza GL, Prabhakar NR (2015) HIF-1alpha activation by intermittent hypoxia requires NADPH oxidase stimulation by xanthine oxidase. PloS One 10:e0119762

    Article  PubMed  PubMed Central  Google Scholar 

  52. Neniskyte U, Fricker M, Brown GC (2016) Amyloid beta induces microglia to phagocytose neurons via activation of protein kinase Cs and NADPH oxidase. Int J Biochem Cell Biol. doi:10.1016/j.biocel.2016.06.005

    PubMed  Google Scholar 

  53. Neumann K, Farias G, Slachevsky A, Perez P, Maccioni RB (2011) Human platelets tau: a potential peripheral marker for Alzheimer’s disease. J Alzheimers Dis 25:103–109

    CAS  PubMed  Google Scholar 

  54. Obisesan TO (2009) Hypertension and cognitive function. Clin Geriatr Med 25:259–288

    Article  PubMed  PubMed Central  Google Scholar 

  55. Olson L, Humpel C (2010) Growth factors and cytokines/chemokines as surrogate biomarkers in cerebrospinal fluid and blood for diagnosing Alzheimer’s disease and mild cognitive impairment. Exp Geront 45:41–46

    CAS  Article  Google Scholar 

  56. Oudegeest-Sander MH, van Beek AH, Abbink K, Olde Rikkert MG, Hopman MT, Claassen JA (2014) Assessment of dynamic cerebral autoregulation and cerebrovascular CO2 reactivity in ageing by measurements of cerebral blood flow and cortical oxygenation. Exp Physiol 99:586–598

    CAS  Article  PubMed  Google Scholar 

  57. Palmer K, Wang HX, Backman L, Winblad B, Fratiglioni L (2002) Differential evolution of cognitive impairment in nondemented older persons: results from the Kungsholmen project. Am J Psychiatry 159:436–442

    Article  PubMed  Google Scholar 

  58. Part K, Kunnis-Beres K, Poska H, Land T, Shimmo R, Zetterstrom Fernaeus S (2015) Amyloid beta25-35 induced ROS-burst through NADPH oxidase is sensitive to iron chelation in microglial Bv2 cells. Brain Res 1629:282–290

    CAS  Article  PubMed  Google Scholar 

  59. Pater C (2011) Mild cognitive impairment (MCI)—the novel trend of targeting Alzheimer’s disease in its early stages—methodological considerations. Curr Alzheimer Res 8:798–807

    CAS  Article  PubMed  Google Scholar 

  60. Pereira AC, Huddleston DE, Brickman AM, Sosunov AA, Hen R, McKhann GM, Sloan R, Gage FH, Brown TR, Small SA (2007) An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci USA 104:5638–5643

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  61. Piret JP, Minet E, Cosse JP, Ninane N, Debacq C, Raes M, Michiels C (2005) Hypoxia-inducible factor-1-dependent overexpression of myeloid cell factor-1 protects hypoxic cells against tert-butyl hydroperoxide-induced apoptosis. J Biol Chem 280:9336–9344

    CAS  Article  PubMed  Google Scholar 

  62. Pratico D, Clark CM, Lee VM, Trojanowski JQ, Rokach J, FitzGerald GA (2000) Increased 8,12-iso-iPF2alpha-VI in Alzheimer’s disease: correlation of a noninvasive index of lipid peroxidation with disease severity. Ann Neurol 48:809–812

    CAS  Article  PubMed  Google Scholar 

  63. Pratico D, Clark CM, Liun F, Rokach J, Lee VY, Trojanowski JQ (2002) Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease. Arch Neurol 59:972–976

    Article  PubMed  Google Scholar 

  64. Price JL, Morris JC (1999) Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol 45:358–368

    CAS  Article  PubMed  Google Scholar 

  65. Rabinowitz MH (2013) Inhibition of hypoxia-inducible factor prolyl hydroxylase domain oxygen sensors: tricking the body into mounting orchestrated survival and repair responses. J Med Chem 56:9369–9402

    CAS  Article  PubMed  Google Scholar 

  66. Reed-Geaghan EG, Savage JC, Hise AG, Landreth GE (2009) CD14 and toll-like receptors 2 and 4 are required for fibrillar A{beta}-stimulated microglial activation. J Neurosci Off J Soc Neurosci 29:11982–11992

    CAS  Article  Google Scholar 

  67. Retz W, Gsell W, Munch G, Rosler M, Riederer P (1998) Free radicals in Alzheimer’s disease. J Neural Transm Suppl 54:221–236

    CAS  Article  PubMed  Google Scholar 

  68. Rodriguez CJ, Bartz TM, Longstreth WT Jr, Kizer JR, Barasch E, Lloyd-Jones DM, Gottdiener JS (2011) Association of annular calcification and aortic valve sclerosis with brain findings on magnetic resonance imaging in community dwelling older adults: the cardiovascular health study. J Am Coll Cardiol 57:2172–2180

    Article  PubMed  PubMed Central  Google Scholar 

  69. Rowley JW, Schwertz H, Weyrich AS (2012) Platelet mRNA: the meaning behind the message. Curr Opin Hematol 19:385–391

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  70. Schofield CJ, Ratcliffe PJ (2004) Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol 5:343–354

    CAS  Article  PubMed  Google Scholar 

  71. Semenza GL (2004) Hydroxylation of HIF-1: oxygen sensing at the molecular level. Physiology 19:176–182

    CAS  Article  PubMed  Google Scholar 

  72. Shiota S, Takekawa H, Matsumoto SE, Takeda K, Nurwidya F, Yoshioka Y, Takahashi F, Hattori N, Tabira T, Mochizuki H et al (2013) Chronic intermittent hypoxia/reoxygenation facilitate amyloid-beta generation in mice. J Alzheimers Dis 37:325–333

    CAS  PubMed  Google Scholar 

  73. Silva DF, Selfridge JE, Lu J, Roy EL, Hutfles L, Burns JM, Michaelis EK, Yan S, Cardoso SM et al (2013) Bioenergetic flux, mitochondrial mass and mitochondrial morphology dynamics in AD and MCI cybrid cell lines. Hum Mol Genet 22:3931–3946

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  74. Silverman DH, Small GW, Chang CY, Lu CS, De Aburto KMA, Chen W, Czernin J, Rapoport SI, Pietrini P, Alexander GE et al (2001) Positron emission tomography in evaluation of dementia: regional brain metabolism and long-term outcome. JAMA 286:2120–2127

    CAS  Article  PubMed  Google Scholar 

  75. Sorond FA, Shaffer ML, Kung AL, Lipsitz LA (2009) Desferroxamine infusion increases cerebral blood flow: a potential association with hypoxia-inducible factor-1. Clin Sci 116:771–779

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  76. Sorond FA, Tan CO, LaRose S, Monk AD, Fichorova R, Ryan S, Lipsitz LA (2015) Deferoxamine, cerebrovascular hemodynamics, and vascular aging: potential role for hypoxia-inducible transcription factor-1-regulated pathways. Stroke J Cereb Circ 46:2576–2583

    CAS  Article  Google Scholar 

  77. Soucek T, Cumming R, Dargusch R, Maher P, Schubert D (2003) The regulation of glucose metabolism by HIF-1 mediates a neuroprotective response to amyloid beta peptide. Neuron 39:43–56

    CAS  Article  PubMed  Google Scholar 

  78. Swindell WR, Johnston A, Xing X, Little A, Robichaud P, Voorhees JJ, Fisher G, Gudjonsson JE (2013) Robust shifts in S100a9 expression with aging: a novel mechanism for chronic inflammation. Sci Rep 3:1215

    Article  PubMed  PubMed Central  Google Scholar 

  79. Tang K, Xia FC, Wagner PD, Breen EC (2010) Exercise-induced VEGF transcriptional activation in brain, lung and skeletal muscle. Respir Physiol Neurobiol 170:16–22

    CAS  Article  PubMed  Google Scholar 

  80. Tsai CK, Kao TW, Lee JT, Wu CJ, Hueng DY, Liang CS, Wang GC, Yang FC, Chen WL (2016) Increased risk of cognitive impairment in patients with components of metabolic syndrome. Medicine 95:e4791

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  81. Valla J, Schneider L, Niedzielko T, Coon KD, Caselli R, Sabbagh MN, Ahern GL, Baxter L, Alexander G, Walker DG et al (2006) Impaired platelet mitochondrial activity in Alzheimer’s disease and mild cognitive impairment. Mitochondrion 6:323–330

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  82. Veitinger M, Varga B, Guterres SB, Zellner M (2014) Platelets, a reliable source for peripheral Alzheimer’s disease biomarkers? Acta Neuropathol Commun 2:65

    Article  PubMed  PubMed Central  Google Scholar 

  83. Vitte J, Michel BF, Bongrand P, Gastaut JL (2004) Oxidative stress level in circulating neutrophils is linked to neurodegenerative diseases. J Clin Immunol 24:683–692

    Article  PubMed  Google Scholar 

  84. Vlassenko AG, Mintun MA, Xiong C, Sheline YI, Goate AM, Benzinger TL, Morris JC (2011) Amyloid-beta plaque growth in cognitively normal adults: longitudinal [11C]Pittsburgh compound B data. Ann Neurol 70:857–861

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  85. Wang Z, Das SR, Xie SX, Arnold SE, Detre JA, Wolk DA, Alzheimer’s Disease Neuroimaging, I. (2013) Arterial spin labeled MRI in prodromal Alzheimer’s disease: a multi-site study. Neuroimage Clin 2:630–636

    Article  PubMed  PubMed Central  Google Scholar 

  86. Xing J, Lu J (2016) HIF-1 alpha activation attenuates IL-6 and TNF-alpha pathways in hippocampus of rats following transient global ischemia. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol 39:511–520

    CAS  Article  Google Scholar 

  87. Yankner BA, Duffy LK, Kirschner DA (1990) Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides. Science 250:279–282

    CAS  Article  PubMed  Google Scholar 

  88. Yeh SH, Hung JJ, Gean PW, Chang WC (2008) Hypoxia-inducible factor-1alpha protects cultured cortical neurons from lipopolysaccharide-induced cell death via regulation of NR1 expression. J Neurosci Off J Soc Neurosci 28:14259–14270

    CAS  Article  Google Scholar 

  89. Yu Q, Fang D, Swerdlow RH, Yu H, Chen JX, Yan SS (2016) Antioxidants rescue mitochondrial transport in differentiated Alzheimer’s disease trans-mitochondrial cybrid cells. J Alzheimers Dis 54:679–690

    CAS  Article  PubMed  Google Scholar 

  90. Yuan G, Nanduri J, Khan S, Semenza GL, Prabhakar NR (2008) Induction of HIF-1alpha expression by intermittent hypoxia: involvement of NADPH oxidase, Ca2+ signaling, prolyl hydroxylases, and mTOR. J Cell Physiol 217:674–685

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  91. Yuan G, Khan SA, Luo W, Nanduri J, Semenza GL, Prabhakar NR (2011) Hypoxia-inducible factor 1 mediates increased expression of NADPH oxidase-2 in response to intermittent hypoxia. J Cell Physiol 226:2925–2933

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  92. Zhang L, Li L, Liu H, Prabhakaran K, Zhang X, Borowitz JL, Isom GE (2007a) HIF-1alpha activation by a redox-sensitive pathway mediates cyanide-induced BNIP3 upregulation and mitochondrial-dependent cell death. Free Radic Biol Med 43:117–127

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  93. Zhang S, Zhang Z, Sandhu G, Ma X, Yang X, Geiger JD, Kong J (2007b) Evidence of oxidative stress-induced BNIP3 expression in amyloid beta neurotoxicity. Brain Res 1138:221–230

    CAS  Article  PubMed  Google Scholar 

  94. Zhang X, Zhou K, Wang R, Cui J, Lipton SA, Liao FF, Xu H, Zhang YW (2007c) Hypoxia-inducible factor 1alpha (HIF-1alpha)-mediated hypoxia increases BACE1 expression and beta-amyloid generation. J Biol Chem 282:10873–10880

    CAS  Article  PubMed  Google Scholar 

  95. Zhang H, Bosch-Marce M, Shimoda LA, Tan YS, Baek JH, Wesley JB, Gonzalez FJ, Semenza GL (2008) Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem 283:10892–10903

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  96. Zhang Z, Yan J, Chang Y, ShiDu Yan S, Shi H (2011) Hypoxia inducible factor-1 as a target for neurodegenerative diseases. Curr Med Chem 18:4335–4343

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  97. Zhou J, Fandrey J, Schumann J, Tiegs G, Brune B (2003) NO and TNF-alpha released from activated macrophages stabilize HIF-1alpha in resting tubular LLC-PK1 cells. Am J Physiol Cell Physiol 284:C439–446

    CAS  Article  PubMed  Google Scholar 

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Acknowledgements

This work was supported by Grants R01 5R01AG31517-2 and 5R01AG045058-01A1 from the National Institute on Aging at the National Institutes of Health (NIH) to Obisesan TO and in part by Grant # UL1TR000101 from the National Center for Advancing Translational Sciences/NIH through the Clinical and Translational Science Award Program (CTSA). The funders had no role in the design, data collection, and interpretation of this study.

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Correspondence to Thomas O. Obisesan.

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Iyalomhe, O., Swierczek, S., Enwerem, N. et al. The Role of Hypoxia-Inducible Factor 1 in Mild Cognitive Impairment. Cell Mol Neurobiol 37, 969–977 (2017). https://doi.org/10.1007/s10571-016-0440-6

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Keywords

  • Mild cognitive impairment
  • Hypoxia-inducible factor 1
  • Glucose
  • Glycolysis
  • Alzheimer’s disease
  • Reactive oxygen species
  • Inflammation