Home LiteratureArticle Details
PMID: 19166904 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Amyloid precursor protein and alpha synuclein translation, implications for iron and inflammation in neurodegenerative diseases.

Biochimica et biophysica acta ·Vol. 1790 ·No. 7 ·2009-07-00 ·Pages 615-28

Cahill CM, Lahiri DK, Huang X, Rogers JT

Abstract

Recent studies that alleles in the hemochromatosis gene may accelerate the onset of Alzheimer's disease by five years have validated interest in the model in which metals (particularly iron) accelerate disease course. Biochemical and biophysical measurements demonstrated the presence of elevated levels of neurotoxic copper zinc and iron in the brains of AD patients. Intracellular levels of APP holoprotein were shown to be modulated by iron by a mechanism that is similar to the translation control of the ferritin L- and H mRNAs by iron-responsive element (IRE) RNA stem loops in their 5' untranslated regions (5'UTRs). More recently a putative IRE-like sequence was hypothesized present in the Parkinsons's alpha synuclein (ASYN) transcript (see [A.L. Friedlich, R.E. Tanzi, J.T. Rogers, The 5'-untranslated region of Parkinson's disease alpha-synuclein messenger RNA contains a predicted iron responsive element, Mol. Psychiatry 12 (2007) 222-223. [6]]). Together with the demonstration of metal dependent translation of APP mRNA, the involvement of metals in the plaque of AD patients and of increased iron in striatal neurons in the substantia nigra (SN) of Parkinson's disease patients have stimulated the development of metal attenuating agents and iron chelators as a major new therapeutic strategy for the treatment of these neurodegenerative diseases. In the case of AD, metal based therapeutics may ultimately prove more cost effective than the use of an amyloid vaccine as the preferred anti-amyloid therapeutic strategy to ameliorate the cognitive decline of AD patients.

MeSH Terms
Alzheimer Disease/drug therapy,metabolism,pathology Amyloid beta-Protein Precursor/genetics,metabolism Animals Base Sequence Chelating Agents/therapeutic use Ferritins/genetics Homeostasis Humans Inflammation Iron/metabolism,therapeutic use Molecular Sequence Data Neurodegenerative Diseases/genetics Parkinson Disease/genetics Protein Biosynthesis RNA, Messenger/metabolism Receptors, Transferrin/genetics alpha-Synuclein/genetics tau Proteins/metabolism
Chemicals
Amyloid beta-Protein Precursor Chelating Agents RNA, Messenger Receptors, Transferrin alpha-Synuclein tau Proteins Ferritins Iron
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Cahill Catherine M
Neurochemistry Laboratory, Department of Psychiatry-Neuroscience, Massachusetts General Hospital (East), Harvard Medical School, CNY2, Building 149, Charlestown, MA 02129, USA.
Lahiri Debomoy K
Huang Xudong
Rogers Jack T
References (189)
189 references, click to expand
  1. Clinically-silent mutation in the putative iron-responsive element in exon 17 of the beta-amyloid precursor protein gene.
    J Neuropathol Exp Neurol. 1992 Jul;51(4):459-63 PMID: 1619445
  2. Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides.
    Science. 1990 Oct 12;250(4978):279-82 PMID: 2218531
  3. Inhibition of protease-resistant prion protein formation by porphyrins and phthalocyanines.
    Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12117-22 PMID: 9770449
  4. Temporal relations among amyloid beta-peptide-induced free-radical oxidative stress, neuronal toxicity, and neuronal defensive responses.
    J Mol Neurosci. 1998 Dec;11(3):183-97 PMID: 10344789
  5. In vivo reduction of amyloid-beta by a mutant copper transporter.
    Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14193-8 PMID: 14617772
  6. Human iron regulatory protein 2 is easily cleaved in its specific domain: consequences for the haem binding properties of the protein.
    Biochem J. 2007 Dec 15;408(3):429-39 PMID: 17760563
  7. Models of amyloid seeding in Alzheimer's disease and scrapie: mechanistic truths and physiological consequences of the time-dependent solubility of amyloid proteins.
    Annu Rev Biochem. 1997;66:385-407 PMID: 9242912
  8. The 5'-untranslated region of Parkinson's disease alpha-synuclein messengerRNA contains a predicted iron responsive element.
    Mol Psychiatry. 2007 Mar;12(3):222-3 PMID: 17325711
  9. mRNA silencing in erythroid differentiation: hnRNP K and hnRNP E1 regulate 15-lipoxygenase translation from the 3' end.
    Cell. 1997 May 16;89(4):597-606 PMID: 9160751
  10. Drug discovery targeted to the Alzheimer's APP mRNA 5'-untranslated region: the action of paroxetine and dimercaptopropanol.
    J Mol Neurosci. 2003;20(3):267-75 PMID: 14501007
  11. Mutated recombinant human heavy-chain ferritins and myelosuppression in vitro and in vivo: a link between ferritin ferroxidase activity and biological function.
    Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):770-4 PMID: 1992468
  12. An iron-responsive element type II in the 5'-untranslated region of the Alzheimer's amyloid precursor protein transcript.
    J Biol Chem. 2002 Nov 22;277(47):45518-28 PMID: 12198135
  13. HFE mutations and Alzheimer's disease.
    J Alzheimers Dis. 2006 Nov;10(2-3):267-76 PMID: 17119292
  14. Ferritin synthesis in inflammation. II. Mechanism of increased ferritin synthesis.
    Br J Haematol. 1981 Nov;49(3):361-70 PMID: 7295586
  15. Initiation of protein synthesis by the eukaryotic translational apparatus on circular RNAs.
    Science. 1995 Apr 21;268(5209):415-7 PMID: 7536344
  16. Widespread peroxynitrite-mediated damage in Alzheimer's disease.
    J Neurosci. 1997 Apr 15;17(8):2653-7 PMID: 9092586
  17. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.
    Nature. 1991 Feb 21;349(6311):704-6 PMID: 1671712
  18. Assessing p97 as an Alzheimer's disease serum biomarker.
    J Alzheimers Dis. 2001 Jun;3(3):339-344 PMID: 12214055
  19. Iron-regulatory proteins, iron-responsive elements and ferritin mRNA translation.
    Int J Biochem Cell Biol. 1999 Oct;31(10):1139-52 PMID: 10582343
  20. Could Abeta and AbetaPP be Antioxidants?
    J Alzheimers Dis. 2000 Jun;2(2):83-84 PMID: 12214093
  21. Porphyrin and phthalocyanine antiscrapie compounds.
    Science. 2000 Feb 25;287(5457):1503-6 PMID: 10688802
  22. Transforming growth factor-beta 1 potentiates amyloid-beta generation in astrocytes and in transgenic mice.
    J Biol Chem. 2003 May 16;278(20):18408-18 PMID: 12626500
  23. alpha-Synuclein locus triplication causes Parkinson's disease.
    Science. 2003 Oct 31;302(5646):841 PMID: 14593171
  24. Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration.
    Cell. 2005 Nov 4;123(3):383-96 PMID: 16269331
  25. Alzheimer's disease drug discovery targeted to the APP mRNA 5'untranslated region.
    J Mol Neurosci. 2002 Aug-Oct;19(1-2):77-82 PMID: 12212798
  26. Alzheimer's mutation.
    Nature. 1991 Apr 18;350(6319):564 PMID: 1901961
  27. Translational enhancement of H-ferritin mRNA by interleukin-1 beta acts through 5' leader sequences distinct from the iron responsive element.
    Nucleic Acids Res. 1994 Jul 11;22(13):2678-86 PMID: 8041631
  28. Magnetic resonance imaging shows delayed ischemic striatal neurodegeneration.
    Ann Neurol. 2003 Dec;54(6):732-47 PMID: 14681883
  29. Assembly of the alpha-globin mRNA stability complex reflects binary interaction between the pyrimidine-rich 3' untranslated region determinant and poly(C) binding protein alphaCP.
    Mol Cell Biol. 1999 Jul;19(7):4572-81 PMID: 10373506
  30. APP locus duplication in a Finnish family with dementia and intracerebral haemorrhage.
    J Neurol Neurosurg Psychiatry. 2007 Oct;78(10):1158-9 PMID: 17442758
  31. A high-throughput drug screen targeted to the 5'untranslated region of Alzheimer amyloid precursor protein mRNA.
    J Biomol Screen. 2006 Aug;11(5):469-80 PMID: 16928984
  32. Human Abeta1-42 reduces iron-induced toxicity in rat cerebral cortex.
    J Neurosci Res. 2003 Aug 1;73(3):316-23 PMID: 12868065
  33. Copper catalyzed oxidation of Alzheimer Abeta.
    Cell Mol Biol (Noisy-le-grand). 2000 Jun;46(4):777-83 PMID: 10875439
  34. Hemin and related porphyrins inhibit beta-amyloid aggregation.
    FEBS Lett. 1997 Nov 10;417(2):249-51 PMID: 9395306
  35. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE.
    Science. 1999 Oct 22;286(5440):735-41 PMID: 10531052
  36. Thyroid hormone modulates the interaction between iron regulatory proteins and the ferritin mRNA iron-responsive element.
    J Biol Chem. 1996 May 17;271(20):12017-23 PMID: 8662626
  37. Alpha-synuclein induces hyperphosphorylation of Tau in the MPTP model of parkinsonism.
    FASEB J. 2006 Nov;20(13):2302-12 PMID: 17077307
  38. Iron chelators and iron toxicity.
    Alcohol. 2003 Jun;30(2):151-8 PMID: 12957300
  39. Metal specificity of an iron-responsive element in Alzheimer's APP mRNA 5'untranslated region, tolerance of SH-SY5Y and H4 neural cells to desferrioxamine, clioquinol, VK-28, and a piperazine chelator.
    J Neural Transm Suppl. 2006;(71):237-47 PMID: 17447434
  40. A quantitative analysis of isoferritins in select regions of aged, parkinsonian, and Alzheimer's diseased brains.
    J Neurochem. 1995 Aug;65(2):717-24 PMID: 7616228
  41. Translation of the alzheimer amyloid precursor protein mRNA is up-regulated by interleukin-1 through 5'-untranslated region sequences.
    J Biol Chem. 1999 Mar 5;274(10):6421-31 PMID: 10037734
  42. The metallobiology of Alzheimer's disease.
    Trends Neurosci. 2003 Apr;26(4):207-14 PMID: 12689772
  43. RNA therapeutics directed to the non coding regions of APP mRNA, in vivo anti-amyloid efficacy of paroxetine, erythromycin, and N-acetyl cysteine.
    Curr Alzheimer Res. 2006 Jul;3(3):221-7 PMID: 16842099
  44. Poly(A)-tail-promoted translation in yeast: implications for translational control.
    RNA. 1998 Nov;4(11):1321-31 PMID: 9814754
  45. Translational control of 5-aminolevulinate synthase mRNA by iron-responsive elements in erythroid cells.
    J Biol Chem. 1993 Mar 15;268(8):5974-8 PMID: 8449958
  46. Cu(II) potentiation of alzheimer abeta neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction.
    J Biol Chem. 1999 Dec 24;274(52):37111-6 PMID: 10601271
  47. Benefits and risks of deferiprone in iron overload in Thalassaemia and other conditions: comparison of epidemiological and therapeutic aspects with deferoxamine.
    Drug Saf. 2003;26(8):553-84 PMID: 12825969
  48. Rapid responses to oxidative stress mediated by iron regulatory protein.
    EMBO J. 1995 Jun 15;14(12):2917-24 PMID: 7796817
  49. Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages.
    Blood. 2003 Dec 1;102(12):4191-7 PMID: 12907459
  50. Excess capacity of the iron regulatory protein system.
    J Biol Chem. 2007 Aug 24;282(34):24650-9 PMID: 17604281
  51. Folding and turnover of human iron regulatory protein 1 depend on its subcellular localization.
    FEBS J. 2007 Feb;274(4):1083-92 PMID: 17244191
  52. Position is the critical determinant for function of iron-responsive elements as translational regulators.
    Mol Cell Biol. 1992 May;12(5):1959-66 PMID: 1569933
  53. The role of iron in beta amyloid toxicity.
    Biochem Biophys Res Commun. 1995 Nov 13;216(2):702-7 PMID: 7488167
  54. Ferritin translation by interleukin-1and interleukin-6: the role of sequences upstream of the start codons of the heavy and light subunit genes.
    Blood. 1996 Mar 15;87(6):2525-37 PMID: 8630420
  55. Dramatic aggregation of Alzheimer abeta by Cu(II) is induced by conditions representing physiological acidosis.
    J Biol Chem. 1998 May 22;273(21):12817-26 PMID: 9582309
  56. More than just two peas in a pod: common amyloidogenic properties of tau and alpha-synuclein in neurodegenerative diseases.
    Trends Neurosci. 2004 Mar;27(3):129-34 PMID: 15036877
  57. Metals in Alzheimer's and Parkinson's diseases.
    Curr Opin Chem Biol. 2008 Apr;12(2):222-8 PMID: 18342639
  58. Iron-dependent regulation of the divalent metal ion transporter.
    FEBS Lett. 2001 Dec 7;509(2):309-16 PMID: 11741608
  59. Crystal structure of human iron regulatory protein 1 as cytosolic aconitase.
    Structure. 2006 Jan;14(1):129-39 PMID: 16407072
  60. Metal exposure and Alzheimer's pathogenesis.
    J Struct Biol. 2006 Jul;155(1):45-51 PMID: 16503166
  61. Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease.
    Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10540-3 PMID: 1683703
  62. The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity.
    J Neurosci. 2000 Aug 15;20(16):6048-54 PMID: 10934254
  63. Aluminum, iron, and zinc ions promote aggregation of physiological concentrations of beta-amyloid peptide.
    J Neurochem. 1993 Sep;61(3):1171-4 PMID: 8360682
  64. Oxygen and iron regulation of iron regulatory protein 2.
    J Biol Chem. 2003 Oct 10;278(41):40337-42 PMID: 12888568
  65. The integrated role of desferrioxamine and phenserine targeted to an iron-responsive element in the APP-mRNA 5'-untranslated region.
    Ann N Y Acad Sci. 2004 Dec;1035:34-48 PMID: 15681799
  66. Consequences of expressing mutants of the hemochromatosis gene (HFE) into a human neuronal cell line lacking endogenous HFE.
    FASEB J. 2007 Feb;21(2):564-76 PMID: 17194693
  67. FMRP mediates mGluR5-dependent translation of amyloid precursor protein.
    PLoS Biol. 2007 Mar;5(3):e52 PMID: 17298186
  68. Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo.
    Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4162-7 PMID: 12634421
  69. Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer's disease transgenic mice.
    Neuron. 2001 Jun;30(3):665-76 PMID: 11430801
  70. Metal sulfate-mediated induction of pathogenic genes and repression by phenyl butyl nitrone and Feralex-G.
    Neuroreport. 2008 Jan 22;19(2):245-9 PMID: 18185117
  71. Individual dopaminergic neurons show raised iron levels in Parkinson disease.
    Neurology. 2007 May 22;68(21):1820-5 PMID: 17515544
  72. Cytoplasmic protein binds in vitro to a highly conserved sequence in the 5' untranslated region of ferritin heavy- and light-subunit mRNAs.
    Proc Natl Acad Sci U S A. 1988 Apr;85(7):2171-5 PMID: 3127826
  73. Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial.
    Arch Neurol. 2003 Dec;60(12):1685-91 PMID: 14676042
  74. Serum ferritin as a predictor of host response to hepatitis B virus infection.
    Science. 1983 Apr 22;220(4595):423-5 PMID: 6301008
  75. Presence of a "CAGA box" in the APP gene unique to amyloid plaque-forming species and absent in all APLP-1/2 genes: implications in Alzheimer's disease.
    FASEB J. 2004 Aug;18(11):1288-90 PMID: 15208260
  76. Combinatorial mRNA regulation: iron regulatory proteins and iso-iron-responsive elements (Iso-IREs).
    J Biol Chem. 2000 Dec 29;275(52):40659-62 PMID: 11062250
  77. Identification of RNA-binding surfaces in iron regulatory protein-1.
    EMBO J. 1999 Nov 1;18(21):6073-83 PMID: 10545118
  78. Trace amounts of copper in water induce beta-amyloid plaques and learning deficits in a rabbit model of Alzheimer's disease.
    Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):11065-9 PMID: 12920183
  79. Iron-dependent oxidation, ubiquitination, and degradation of iron regulatory protein 2: implications for degradation of oxidized proteins.
    Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4924-8 PMID: 9560204
  80. Copper, iron and zinc in Alzheimer's disease senile plaques.
    J Neurol Sci. 1998 Jun 11;158(1):47-52 PMID: 9667777
  81. Alpha2-macroglobulin enhances the clearance of endogenous soluble beta-amyloid peptide via low-density lipoprotein receptor-related protein in cortical neurons.
    J Neurochem. 1999 Oct;73(4):1393-8 PMID: 10501182
  82. Amyloid plaque core protein in Alzheimer disease and Down syndrome.
    Proc Natl Acad Sci U S A. 1985 Jun;82(12):4245-9 PMID: 3159021
  83. Posttranscriptional regulation of chimeric human transferrin genes by iron.
    Biochemistry. 1993 May 11;32(18):4738-45 PMID: 8490018
  84. Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron, nitric oxide, and oxidative stress.
    Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8175-82 PMID: 8710843
  85. Severity of neurodegeneration correlates with compromise of iron metabolism in mice with iron regulatory protein deficiencies.
    Ann N Y Acad Sci. 2004 Mar;1012:65-83 PMID: 15105256
  86. Ferritin in serum. Clinical and biochemical implications.
    N Engl J Med. 1975 May 1;292(18):951-6 PMID: 1090831
  87. A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid.
    Nat Genet. 1992 Aug;1(5):345-7 PMID: 1302033
  88. Translational repressor activity is equivalent and is quantitatively predicted by in vitro RNA binding for two iron-responsive element-binding proteins, IRP1 and IRP2.
    J Biol Chem. 1995 Mar 10;270(10):4983-6 PMID: 7890603
  89. High levels of Alzheimer beta-amyloid precursor protein (APP) in children with severely autistic behavior and aggression.
    J Child Neurol. 2006 Jun;21(6):444-9 PMID: 16948926
  90. Discovery of compounds that will prevent tau pathology.
    J Mol Neurosci. 2002 Dec;19(3):261-6 PMID: 12540051
  91. Rapid induction of Alzheimer A beta amyloid formation by zinc.
    Science. 1994 Sep 2;265(5177):1464-7 PMID: 8073293
  92. Mfold web server for nucleic acid folding and hybridization prediction.
    Nucleic Acids Res. 2003 Jul 1;31(13):3406-15 PMID: 12824337
  93. Rapid restoration of cognition in Alzheimer's transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta.
    Neuron. 2008 Jul 10;59(1):43-55 PMID: 18614028
  94. p97 as a biomarker for Alzheimer disease.
    Front Biosci. 2002 Feb 01;7:e42-7 PMID: 11815303
  95. Metalloenzyme-like activity of Alzheimer's disease beta-amyloid. Cu-dependent catalytic conversion of dopamine, cholesterol, and biological reducing agents to neurotoxic H(2)O(2).
    J Biol Chem. 2002 Oct 25;277(43):40302-8 PMID: 12192006
  96. Pretranslational modulation of acute phase hepatic protein synthesis by murine recombinant interleukin 1 (IL-1) and purified human IL-1.
    J Exp Med. 1985 Sep 1;162(3):930-42 PMID: 2411843
  97. Aluminum induced oxidative events and its relation to inflammation: a role for the metal in Alzheimer's disease.
    Cell Mol Biol (Noisy-le-grand). 2000 Jun;46(4):721-30 PMID: 10875435
  98. Expression of poly(C)-binding proteins is differentially regulated by hypoxia and ischemia in cortical neurons.
    Neuroscience. 2002;110(2):191-8 PMID: 11958862
  99. Alzheimer's disease in Down's syndrome: clinicopathologic studies.
    Neurology. 1985 Jul;35(7):957-61 PMID: 3159974
  100. Double-knockout mice for alpha- and beta-synucleins: effect on synaptic functions.
    Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14966-71 PMID: 15465911
  101. Interleukin-1alpha stimulates non-amyloidogenic pathway by alpha-secretase (ADAM-10 and ADAM-17) cleavage of APP in human astrocytic cells involving p38 MAP kinase.
    J Neurosci Res. 2006 Jul;84(1):106-18 PMID: 16724341
  102. Alpha-synuclein pathology in Parkinson's and Alzheimer's disease brain: incidence and topographic distribution--a pilot study.
    Acta Neuropathol. 2003 Sep;106(3):191-201 PMID: 12845452
  103. Assembly of the gamma-secretase complex involves early formation of an intermediate subcomplex of Aph-1 and nicastrin.
    J Biol Chem. 2003 Sep 26;278(39):37213-22 PMID: 12857757
  104. Metal and inflammatory targets for Alzheimer's disease.
    Curr Drug Targets. 2004 Aug;5(6):535-51 PMID: 15270200
  105. Alpha-1-antichymotrypsin promotes beta-sheet amyloid plaque deposition in a transgenic mouse model of Alzheimer's disease.
    J Neurosci. 2001 Mar 1;21(5):1444-51 PMID: 11222634
  106. Candidate gene for the chromosome 1 familial Alzheimer's disease locus.
    Science. 1995 Aug 18;269(5226):973-7 PMID: 7638622
  107. Characterization of the APP proximal promoter and 5'-untranslated regions: identification of cell type-specific domains and implications in APP gene expression and Alzheimer's disease.
    FASEB J. 2005 Apr;19(6):653-5 PMID: 15703276
  108. Iron, brain ageing and neurodegenerative disorders.
    Nat Rev Neurosci. 2004 Nov;5(11):863-73 PMID: 15496864
  109. Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration.
    Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18676-81 PMID: 16352719
  110. The Anemia Associated With Chronic Infection.
    Science. 1946 Jan 18;103(2664):72-3 PMID: 17732761
  111. Oxygen toxicity, oxygen radicals, transition metals and disease.
    Biochem J. 1984 Apr 1;219(1):1-14 PMID: 6326753
  112. The hemochromatosis gene affects the age of onset of sporadic Alzheimer's disease.
    Neurobiol Aging. 2001 Jul-Aug;22(4):563-8 PMID: 11445256
  113. Reversible ischemia increases levels of Alzheimer amyloid protein precursor without increasing levels of mRNA in the rabbit spinal cord.
    Brain Res Mol Brain Res. 1997 Oct 3;49(1-2):103-12 PMID: 9387869
  114. Evidence that the beta-amyloid plaques of Alzheimer's disease represent the redox-silencing and entombment of abeta by zinc.
    J Biol Chem. 2000 Jun 30;275(26):19439-42 PMID: 10801774
  115. The A beta peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction.
    Biochemistry. 1999 Jun 15;38(24):7609-16 PMID: 10386999
  116. Mouse brains deficient in H-ferritin have normal iron concentration but a protein profile of iron deficiency and increased evidence of oxidative stress.
    J Neurosci Res. 2003 Jan 1;71(1):46-63 PMID: 12478613
  117. Effects of Coenzyme Q10 in Huntington's disease and early Parkinson's disease.
    Biofactors. 2003;18(1-4):153-61 PMID: 14695931
  118. Copper-induced ferroportin-1 expression in J774 macrophages is associated with increased iron efflux.
    Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2700-5 PMID: 14973193
  119. The C2 variant of human serum transferrin retains the iron binding properties of the native protein.
    Biochim Biophys Acta. 2005 Sep 25;1741(3):264-70 PMID: 15975770
  120. Alzheimer's disease amyloid-beta binds copper and zinc to generate an allosterically ordered membrane-penetrating structure containing superoxide dismutase-like subunits.
    J Biol Chem. 2001 Jun 8;276(23):20466-73 PMID: 11274207
  121. Double-stranded (ds) RNA binding and not dimerization correlates with the activation of the dsRNA-dependent protein kinase (PKR).
    J Biol Chem. 1996 Jan 19;271(3):1756-63 PMID: 8576179
  122. Competition for microtubule-binding with dual expression of tau missense and splice isoforms.
    Mol Biol Cell. 2001 Jan;12(1):171-84 PMID: 11160831
  123. Structure of dual function iron regulatory protein 1 complexed with ferritin IRE-RNA.
    Science. 2006 Dec 22;314(5807):1903-8 PMID: 17185597
  124. Synergy between the C2 allele of transferrin and the C282Y allele of the haemochromatosis gene (HFE) as risk factors for developing Alzheimer's disease.
    J Med Genet. 2004 Apr;41(4):261-5 PMID: 15060098
  125. A GG nucleotide sequence of the 3' untranslated region of amyloid precursor protein mRNA plays a key role in the regulation of translation and the binding of proteins.
    Mol Cell Biol. 2000 Jul;20(13):4572-9 PMID: 10848584
  126. The acute box cis-element in human heavy ferritin mRNA 5'-untranslated region is a unique translation enhancer that binds poly(C)-binding proteins.
    J Biol Chem. 2005 Aug 26;280(34):30032-45 PMID: 15967798
  127. In vivo evaluation of brain iron in Alzheimer disease using magnetic resonance imaging.
    Arch Gen Psychiatry. 2000 Jan;57(1):47-53 PMID: 10632232
  128. Amyloid precursor protein mRNA stability is controlled by a 29-base element in the 3'-untranslated region.
    J Biol Chem. 1994 Sep 30;269(39):24007-13 PMID: 7929051
  129. TGF-beta(1), regulation of alzheimer amyloid precursor protein mRNA expression in a normal human astrocyte cell line: mRNA stabilization.
    Brain Res Mol Brain Res. 1999 Jul 23;71(1):42-9 PMID: 10407185
  130. Deferiprone versus desferrioxamine in thalassaemia, and T2* validation and utility.
    Lancet. 2003 Jan 11;361(9352):183; author reply 183-4 PMID: 12531619
  131. Interleukin 1 administration in mice produces hypoferremia despite neutropenia.
    J Clin Invest. 1988 Dec;82(6):1934-8 PMID: 3264289
  132. Hydroxyl radicals, iron, oxidative stress, and neurodegeneration.
    Ann N Y Acad Sci. 1994 Nov 17;738:201-13 PMID: 7832429
  133. Translational suppression by trinucleotide repeat expansion at FMR1.
    Science. 1995 May 5;268(5211):731-4 PMID: 7732383
  134. Intramuscular desferrioxamine in patients with Alzheimer's disease.
    Lancet. 1991 Jun 1;337(8753):1304-8 PMID: 1674295
  135. Gene knockout of amyloid precursor protein and amyloid precursor-like protein-2 increases cellular copper levels in primary mouse cortical neurons and embryonic fibroblasts.
    J Neurochem. 2004 Oct;91(2):423-8 PMID: 15447675
  136. The amyloid precursor protein of Alzheimer's disease in the reduction of copper(II) to copper(I)
    Science. 1996 Mar 8;271(5254):1406-9 PMID: 8596911
  137. Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease.
    Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11282-6 PMID: 8248242
  138. Dual function of the messenger RNA cap structure in poly(A)-tail-promoted translation in yeast.
    Nature. 1998 Apr 2;392(6675):516-20 PMID: 9548259
  139. Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice.
    Nat Genet. 2001 Feb;27(2):209-14 PMID: 11175792
  140. Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer's disease.
    Am J Pathol. 1994 Jul;145(1):42-7 PMID: 8030754
  141. Ferritin is a component of the neuritic (senile) plaque in Alzheimer dementia.
    Acta Neuropathol. 1990;81(2):105-10 PMID: 2082650
  142. Coordinate transcriptional and translational regulation of ferritin in response to oxidative stress.
    Mol Cell Biol. 2000 Aug;20(16):5818-27 PMID: 10913165
  143. APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy.
    Nat Genet. 2006 Jan;38(1):24-6 PMID: 16369530
  144. Starting at the beginning, middle, and end: translation initiation in eukaryotes.
    Cell. 1997 Jun 13;89(6):831-8 PMID: 9200601
  145. Amyloid beta-peptide is produced by cultured cells during normal metabolism.
    Nature. 1992 Sep 24;359(6393):322-5 PMID: 1383826
  146. Hypoxia alters iron-regulatory protein-1 binding capacity and modulates cellular iron homeostasis in human hepatoma and erythroleukemia cells.
    J Biol Chem. 1999 Feb 12;274(7):4467-73 PMID: 9933651
  147. Pharmacological strategies for the prevention of Alzheimer's disease.
    Expert Opin Pharmacother. 2006 Jan;7(1):1-10 PMID: 16370917
  148. Alpha 1-antichymotrypsin is present together with the beta-protein in monkey brain amyloid deposits.
    Neuroscience. 1989;32(3):715-20 PMID: 2689908
  149. Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease.
    Neuron. 2003 Mar 27;37(6):899-909 PMID: 12670420
  150. Mitochondria, oxidative damage, and inflammation in Parkinson's disease.
    Ann N Y Acad Sci. 2003 Jun;991:120-31 PMID: 12846981
  151. GATA transcription factors directly regulate the Parkinson's disease-linked gene alpha-synuclein.
    Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10907-12 PMID: 18669654
  152. Human erythroid 5-aminolevulinate synthase: promoter analysis and identification of an iron-responsive element in the mRNA.
    EMBO J. 1991 Jul;10(7):1891-902 PMID: 2050125
  153. Iron: a pathological mediator of Alzheimer disease?
    Dev Neurosci. 2002;24(2-3):184-7 PMID: 12401957
  154. Copper depletion down-regulates expression of the Alzheimer's disease amyloid-beta precursor protein gene.
    J Biol Chem. 2004 May 7;279(19):20378-86 PMID: 14985339
  155. Growth factor-mediated stabilization of amyloid precursor protein mRNA is mediated by a conserved 29-nucleotide sequence in the 3'-untranslated region.
    J Neurochem. 2000 Jan;74(1):52-9 PMID: 10617105
  156. Secretion of ferritin by rat hepatoma cells and its regulation by inflammatory cytokines and iron.
    Blood. 1997 Dec 15;90(12):4979-86 PMID: 9389717
  157. Regional distribution of iron and iron-regulatory proteins in the brain in aging and Alzheimer's disease.
    J Neurosci Res. 1992 Feb;31(2):327-35 PMID: 1573683
  158. Evidence that tumor necrosis factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor.
    J Biol Chem. 1998 Oct 23;273(43):27765-7 PMID: 9774383
  159. Interleukin-1beta increases binding of the iron regulatory protein and the synthesis of ferritin by increasing the labile iron pool.
    Biochim Biophys Acta. 2000 Sep 20;1497(3):279-88 PMID: 10996652
  160. Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database.
    Nat Genet. 2007 Jan;39(1):17-23 PMID: 17192785
  161. Amyloid beta-protein and the genetics of Alzheimer's disease.
    J Biol Chem. 1996 Aug 2;271(31):18295-8 PMID: 8756120
  162. Characterization of sorting signals in the beta-amyloid precursor protein cytoplasmic domain.
    J Biol Chem. 1995 Feb 24;270(8):3565-73 PMID: 7876092
  163. The role of iron regulatory proteins in mammalian iron homeostasis and disease.
    Nat Chem Biol. 2006 Aug;2(8):406-14 PMID: 16850017
  164. Reduction of iron-regulated amyloid precursor protein and beta-amyloid peptide by (-)-epigallocatechin-3-gallate in cell cultures: implications for iron chelation in Alzheimer's disease.
    J Neurochem. 2006 Apr;97(2):527-36 PMID: 16539659
  165. Framing beta-amyloid.
    Nat Genet. 1992 Jul;1(4):233-4 PMID: 1363811
  166. Apolipoprotein E, survival in Alzheimer's disease patients, and the competing risks of death and Alzheimer's disease.
    Neurology. 1995 Jul;45(7):1323-8 PMID: 7617191
  167. A novel iron uptake mechanism mediated by GPI-anchored human p97.
    EMBO J. 1995 Sep 1;14(17):4178-86 PMID: 7556058
  168. The oligomerization of amyloid beta-protein begins intracellularly in cells derived from human brain.
    Biochemistry. 2000 Sep 5;39(35):10831-9 PMID: 10978169
  169. Transferrin C2 variant does confer a risk for Alzheimer's disease in caucasians.
    J Alzheimers Dis. 2003 Dec;5(6):423-7 PMID: 14757931
  170. FDA-preapproved drugs targeted to the translational regulation and processing of the amyloid precursor protein.
    J Mol Neurosci. 2004;24(1):129-36 PMID: 15314261
  171. A histochemical study of iron, transferrin, and ferritin in Alzheimer's diseased brains.
    J Neurosci Res. 1992 Jan;31(1):75-83 PMID: 1613823
  172. Overexpression of superoxide dismutase 1 protects against beta-amyloid peptide toxicity: effect of estrogen and copper chelators.
    Neurochem Int. 2004 Jan;44(1):25-33 PMID: 12963085
  173. Presenilin 1 is required for Notch1 and DII1 expression in the paraxial mesoderm.
    Nature. 1997 May 15;387(6630):288-92 PMID: 9153393
  174. IRP-1 binding to ferritin mRNA prevents the recruitment of the small ribosomal subunit by the cap-binding complex eIF4F.
    Mol Cell. 1998 Sep;2(3):383-8 PMID: 9774976
  175. Alterations in the interaction between iron regulatory proteins and their iron responsive element in normal and Alzheimer's diseased brains.
    Cell Mol Biol (Noisy-le-grand). 2000 Jun;46(4):761-76 PMID: 10875438
  176. Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity.
    Nature. 1999 Apr 8;398(6727):513-7 PMID: 10206644
  177. Role of cytokines in the gene expression of amyloid beta-protein precursor: identification of a 5'-UTR-binding nuclear factor and its implications in Alzheimer's disease.
    J Alzheimers Dis. 2003 Apr;5(2):81-90 PMID: 12719626
  178. Direct and potent regulation of gamma-secretase by its lipid microenvironment.
    J Biol Chem. 2008 Aug 15;283(33):22529-40 PMID: 18539594
  179. Ferritin: a cytoprotective antioxidant strategem of endothelium.
    J Biol Chem. 1992 Sep 5;267(25):18148-53 PMID: 1517245
  180. Alternative polyadenylation of the amyloid protein precursor mRNA regulates translation.
    EMBO J. 1992 Aug;11(8):3099-103 PMID: 1353447
  181. Translational control during the acute phase response. Ferritin synthesis in response to interleukin-1.
    J Biol Chem. 1990 Aug 25;265(24):14572-8 PMID: 1696948
  182. A novel trivalent cation chelator Feralex dissociates binding of aluminum and iron associated with hyperphosphorylated tau of Alzheimer's disease.
    Brain Res. 2003 Jan 24;961(1):139-46 PMID: 12535786
  183. Thyrotropin-releasing hormone and epidermal growth factor regulate iron-regulatory protein binding in pituitary cells via protein kinase C-dependent and -independent signaling pathways.
    J Biol Chem. 2000 Oct 13;275(41):31609-15 PMID: 10889193
  184. Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid Abeta production in APP23 transgenic mice.
    Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14187-92 PMID: 14617773
  185. Role of the APP non-amyloidogenic signaling pathway and targeting alpha-secretase as an alternative drug target for treatment of Alzheimer's disease.
    Curr Med Chem. 2007;14(27):2848-64 PMID: 18045131
  186. Aph-1, Pen-2, and Nicastrin with Presenilin generate an active gamma-Secretase complex.
    Neuron. 2003 Apr 10;38(1):9-12 PMID: 12691659
  187. Alpha-synuclein and chaperones in dementia with Lewy bodies.
    J Neuropathol Exp Neurol. 2005 Dec;64(12):1058-66 PMID: 16319716
  188. Deferiprone and hepatic fibrosis.
    Blood. 2003 Jun 15;101(12):5089-90; author reply 5090-1 PMID: 12788794
  189. Modulation of cellular iron metabolism by hydrogen peroxide. Effects of H2O2 on the expression and function of iron-responsive element-containing mRNAs in B6 fibroblasts.
    J Biol Chem. 2001 Jun 8;276(23):19738-45 PMID: 11264285
Article Info
Journal
Biochimica et biophysica acta
Abbr.
Biochim Biophys Acta
ISSN
0006-3002
DOI
10.1016/j.bbagen.2008.12.001
Published
2009-07-00
Epub
2008-00-29
Pages
615-28
Language
English
Region
Netherlands
NLM ID
0217513
PMCID
PMC3981543
Subset
IM
Grants
NINDS NIH HHS · R21 NS059434 · United States
NIA NIH HHS · AG02081 · United States
External Links
PubMed source DOI: 10.1016/j.bbagen.2008.12.001 PMC Full Text
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2