Iron Dyshomeostasis Induces Binding of APP to BACE1 for Amyloid Pathology, and Impairs APP/Fpn1 Complex in Microglia: Implication in Pathogenesis of Cerebral Microbleeds

Cell Transplantation

Volumn 28, Issue 8, 2019, Pages 1009-1017

  Gong, Li ^a   Tian, Xiangzhu ^a   Zhou, Jing ^b   Dong, Qiong ^a   Tan, Yan ^a   Lu, You ^a   Wu, Jiayan ^a   Zhao, Yanxin ^a   Liu, Xueyuan ^a  

^a TONGJI UNIVERSITY   (China)

^b Binhai County People s Hospital   (China)

Author keywords

amyloid protein precursor; cerebral microbleeds; ferritin; iron; small vessel disease

Indexed keywords

AMYLOID; AMYLOID BETA PROTEIN[1-42]; AMYLOID PRECURSOR PROTEIN; BETA ACTIN; BETA SECRETASE 1; FERRIC CHLORIDE; FERRITIN; IRON; MESSENGER RNA; ASPARTIC PROTEINASE; BACE1 PROTEIN, MOUSE; CATION TRANSPORT PROTEIN; METAL TRANSPORTING PROTEIN 1; PROTEIN BINDING; SECRETASE;

ANIMAL TISSUE; ARTICLE; BRAIN HEMORRHAGE; COGNITIVE DEFECT; ENZYME LINKED IMMUNOSORBENT ASSAY; IRON HOMEOSTASIS; MICROGLIA; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN METABOLISM; REAL TIME POLYMERASE CHAIN REACTION; WESTERN BLOTTING; ANIMAL; CELL LINE; GENETICS; HOMEOSTASIS; METABOLISM; MOUSE; PATHOLOGY;

AMYLOID; AMYLOID BETA-PROTEIN PRECURSOR; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ASPARTIC ACID ENDOPEPTIDASES; CATION TRANSPORT PROTEINS; CELL LINE; CEREBRAL HEMORRHAGE; HOMEOSTASIS; IRON; MICE; MICROGLIA; PROTEIN BINDING; RNA, MESSENGER;

EID: 85071771840     PISSN: 09636897     EISSN: 15553892     Source Type: Journal    
DOI: 10.1177/0963689719831707     Document Type: Article

References (32)

1. Fazekas F, Kleinert R, Roob G, Kleinert G, Kapeller P, Schmidt R, Hartung HP. Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds. AJNR Am J Neuroradiol. 1999;20(4):637–642.
2. Schrag M, McAuley G, Pomakian J, Jiffry A, Tung S, Mueller C, Vinters HV, Haacke EM, Holshouser B, Kido D, Kirsch WM. Correlation of hypointensities in susceptibility-weighted images to tissue histology in dementia patients with cerebral amyloid angiopathy: a postmortem MRI study. Acta Neuropathol. 2010;119(3):291–302.
3. Liu Y, Liu J, Liu H, Liao Y, Cao L, Ye B, Wang W. Investigation of cerebral iron deposition in aged patients with ischemic cerebrovascular disease using susceptibility-weighted imaging. Ther Clin Risk Manag. 2016;12:1239–1247.
4. Ping S, Qiu X, Gonzalez-Toledo ME, Liu X, Zhao LR. Stem cell factor in combination with granulocyte colony-stimulating factor reduces cerebral capillary thrombosis in a mouse model of CADASIL. Cell Transplant. 2018;27(4):637–647.
5. Goos JD, Kester MI, Barkhof F, Klein M, Blankenstein MA, Scheltens P, van der Flier WM. Patients with Alzheimer disease with multiple microbleeds: relation with cerebrospinal fluid biomarkers and cognition. Stroke. 2009;40(11):3455–3460.
6. Kester MI, van der Flier WM, Mandic G, Blankenstein MA, Scheltens P, Muller M. Joint effect of hypertension and APOE genotype on CSF biomarkers for Alzheimer’s disease. J Alzheimers Dis. 2010;20(4):1083–1090.
7. Cordonnier C, van der Flier WM. Brain microbleeds and Alzheimer’s disease: innocent observation or key player? Brain. 2011;134(Pt 2):335–344.
8. Kester MI, Goos JD, Teunissen CE, Benedictus MR, Bouwman FH, Wattjes MP, Barkhof F, Scheltens P, van der Flier WM. Associations between cerebral small-vessel disease and Alzheimer disease pathology as measured by cerebrospinal fluid biomarkers. JAMA Neurol. 2014;71(7):855–862.
9. Shams S, Granberg T, Martola J, Li X, Shams M, Fereshtehnejad SM, Cavallin L, Aspelin P, Kristoffersen-Wiberg M, Wahlund LO. Cerebrospinal fluid profiles with increasing number of cerebral microbleeds in a continuum of cognitive impairment. J Cereb Blood Flow Metab. 2016;36(3):621–628.
10. Ayton S, Faux NG, Bush AI,; Alzheimer’s disease neuroimaging initiative. Ferritin levels in the cerebrospinal fluid predict Alzheimer’s disease outcomes and are regulated by APOE. Nat Commun. 2015;6:6760.
11. Bandyopadhyay S, Rogers JT. Alzheimer’s disease therapeutics targeted to the control of amyloid precursor protein translation: maintenance of brain iron homeostasis. Biochem Pharmacol. 2014;88(4):486–494.
12. Ehrhart J, Darlington D, Kuzmin-Nichols N, Sanberg CD, Sawmiller DR, Sanberg PR, Tan J. Biodistribution of infused human umbilical cord blood cells in Alzheimer’s disease-like murine model. Cell Transplant. 2016;25(1):195–199.
13. Fujioka M, Taoka T, Matsuo Y, Mishima K, Ogoshi K, Kondo Y. Magnetic resonance imaging shows delayed ischemic striatal neurodegeneration. Ann Neurol. 2003;54(6):732–747.
14. Rogers JT, Venkataramani V, Washburn C, Liu Y, Tummala V, Jiang H, Smith A, Cahill CM. A role for amyloid precursor protein translation to restore iron homeostasis and ameliorate lead (Pb) neurotoxicity. J Neurochem. 2016;138(3):479–494.
15. Duce JA, Tsatsanis A, Cater MA, James SA, Robb E, Wikhe K, Leong SL, Perez K, Johanssen T, Greenough MA, Cho HH, Galatis D, Moir RD, Masters CL, McLean C, Tanzi RE, Cappai R, Barnham KJ, Ciccotosto GD, Rogers JT, Bush AI. Iron-export ferroxidase activity of β-amyloid precursor protein is inhibited by zinc in Alzheimer’s disease. Cell. 2010;142(6):857–867.
16. Lei P, Ayton S, Finkelstein DI, Spoerri L, Ciccotosto GD, Wright DK, Wong BX, Adlard PA, Cherny RA, Lam LQ, Roberts BR, Volitakis I, Egan GF, McLean CA, Cappai R, Duce JA, Bush AI. Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export. Nat Med. 2012;18(2):291–295.
17. Banati RB, Gehrmann J, Lannes-Vieira J, Wekerle H, Kreutzberg GW. Inflammatory reaction in experimental autoimmune encephalomyelitis (EAE) is accompanied by a microglial expression of the beta A4-amyloid precursor protein (APP). Glia. 1995;14(3):209–215.
18. Banati RB, Gehrmann J, Czech C, Mönning U, Jones LL, König G, Beyreuther K, Kreutzberg GW. Early and rapid de novo synthesis of Alzheimer beta A4-amyloid precursor protein (APP) in activated microglia. Glia. 1993;9(3):199–210.
19. Moisan A, Favre I, Rome C, De Fraipont F, Grillon E, Coquery N, Mathieu H, Mayan V, Naegele B, Hommel M, Richard MJ, Barbier EL, Remy C, Detante O. Intravenous injection of clinical grade human MSCs after experimental stroke: functional benefit and microvascular effect. Cell Transplant. 2016;25(12):2157–2171.
20. Lopes KO, Sparks DL, Streit WJ. Microglial dystrophy in the aged and Alzheimer’s disease brain is associated with ferritin immunoreactivity. Glia. 2008;56(10):1048–1060.
21. Honda K, Casadesus G, Petersen RB, Perry G, Smith MA. Oxidative stress and redox-active iron in Alzheimer’s disease. Ann N Y Acad Sci. 2004;1012:179–182.
22. Casadesus G, Smith MA, Zhu X, Aliev G, Cash AD, Honda K, Petersen RB, Perry G. Alzheimer disease: evidence for a central pathogenic role of iron-mediated reactive oxygen species. J Alzheimers Dis. 2004;6(2):165–169.
23. Moreira PI, Siedlak SL, Aliev G, Zhu X, Cash AD, Smith MA, Perry G. Oxidative stress mechanisms and potential therapeutics in Alzheimer disease. J Neural Transm. 2005;112(7):921–932.
24. Chang YH, Wu KC, Harn HJ, Lin SZ, Ding DC. Exosomes and stem cells in degenerative disease diagnosis and therapy. Cell Transplant. 2018;27(3):349–363.
25. Avramovich-Tirosh Y, Amit T, Bar-Am O, Weinreb O, Youdim MB. Physiological and pathological aspects of Aβ in iron homeostasis via 5’UTR in the APP mRNA and the therapeutic use of iron-chelators. BMC Neurosci. 2008;9(Suppl 2):S2.
26. Cho HH, Cahill CM, Vanderburg CR, Scherzer CR, Wang B, Huang X, Rogers JT. Selective translational control of the Alzheimer amyloid precursor protein transcript by iron regulatory protein-1. J Biol Chem. 2010;285(41):31217–31232.
27. Manocha GD, Floden AM, Rausch K, Kulas JA, McGregor BA, Rojanathammanee L, Puig KR, Puig KL, Karki S, Nichols MR, Darland DC, Porter JE, Combs CK. APP regulates microglial phenotype in a mouse model of Alzheimer’s disease. J Neurosci. 2016;36(32):8471–8486.
28. Mehlhase J, Sandig G, Pantopoulos K, Grune T. Oxidation-induced ferritin turnover in microglial cells: role of proteasome. Free Radical Biol Med. 2005;38(2):276–285.
29. Mehlhase J, Gieche J, Widmer R, Grune T. Ferritin levels in microglia depend upon activation: modulation by reactive oxygen species. Biochim Biophys Acta. 2006;1763(8):854–859.
30. Rathore KI, Redensek A, David S. Iron homeostasis in astrocytes and microglia is differentially regulated by TNF-α and TGF-β1. Glia. 2012;60(5):738–750.
31. Urrutia P, Aguirre P, Esparza A, Tapia V, Mena NP, Arredondo M, González-Billault C, Núñez MT. Inflammation alters the expression of DMT1, Fpn1 and hepcidin, and it causes iron accumulation in central nervous system cells. J Neurochem. 2013;126(4):541–549.
32. Li Y, Pan K, Chen L Ning JL, Li X, Yang T, Terrando N, Gu J, Tao GJ. Deferoxamine regulates neuroinflammation and iron homeostasis in a mouse model of postoperative cognitive dysfunction. J Neuroinflammation. 2016;13(1):268.