Generic placeholder image

Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Perspective

Dysregulation of Neuronal Iron in Alzheimer’s Disease

Author(s): Md. Sahab Uddin and Ghulam Md Ashraf*

Volume 21, Issue 11, 2023

Published on: 31 August, 2022

Page: [2247 - 2250] Pages: 4

DOI: 10.2174/1570159X20666211231163544

conference banner
[1]
Gerlach, M.; Ben-Shachar, D.; Riederer, P.; Youdim, M.B.H. Altered brain metabolism of iron as a cause of neurodegenerative diseases? J. Neurochem., 1994, 63(3), 793-807.
[http://dx.doi.org/10.1046/j.1471-4159.1994.63030793.x] [PMID: 7519659]
[2]
Mu, Q.; Chen, L.; Gao, X.; Shen, S.; Sheng, W.; Min, J.; Wang, F. The role of iron homeostasis in remodeling immune function and regulating inflammatory disease. Sci. Bull. (Beijing), 2021, 66, 1806-1816.
[http://dx.doi.org/10.1016/j.scib.2021.02.010]
[3]
Wang, Y.; Wu, Y.; Li, T.; Wang, X.; Zhu, C. Iron metabolism and brain development in premature infants. Front. Physiol., 2019, 10, 463.
[http://dx.doi.org/10.3389/fphys.2019.00463] [PMID: 31105583]
[4]
Yan, N.; Zhang, J. Iron Metabolism, Ferroptosis, and the Links With Alzheimer’s Disease. Front. Neurosci., 2019, 13.
[PMID: 32063824]
[5]
Razmeh, S.; Habibi, A.H.; Orooji, M.; Alizadeh, E.; Moradiankokhdan, K.; Razmeh, B. Pantothenate kinase-associated neurodegeneration: Clinical aspects, diagnosis and treatments. Neurol. Int., 2018, 10(1), 7516.
[http://dx.doi.org/10.4081/ni.2018.7516] [PMID: 29844889]
[6]
Sina, F.; Shojaee, S.; Elahi, E.; Paisán-Ruiz, C. R632W mutation in PLA2G6 segregates with dystonia-parkinsonism in a consanguineous Iranian family. Eur. J. Neurol., 2009, 16(1), 101-104.
[http://dx.doi.org/10.1111/j.1468-1331.2008.02356.x] [PMID: 19087156]
[7]
Paisan-Ruiz, C.; Bhatia, K.P.; Li, A.; Hernandez, D.; Davis, M.; Wood, N.W.; Hardy, J.; Houlden, H.; Singleton, A.; Schneider, S.A. Characterization of PLA2G6 as a locus for dystonia-parkinsonism. Ann. Neurol., 2009, 65(1), 19-23.
[http://dx.doi.org/10.1002/ana.21415] [PMID: 18570303]
[8]
Kabir, M.T.; Uddin, M.S.; Zaman, S.; Begum, Y.; Ashraf, G.M.; Bin-Jumah, M.N.; Bungau, S.G.; Mousa, S.A.; Abdel-Daim, M.M. Molecular mechanisms of metal toxicity in the pathogenesis of Alzheimer’s disease. Mol Neurobiol, 2021, 58(1), 1-20.
[http://dx.doi.org/10.1007/s12035-020-02096-w] [PMID: 32889653]
[9]
Tsatsanis, A.; McCorkindale, A.N.; Wong, B.X.; Patrick, E.; Ryan, T.M.; Evans, R.W.; Bush, A.I.; Sutherland, G.T.; Sivaprasadarao, A.; Guennewig, B.; Duce, J.A. The acute phase protein lactoferrin is a key feature of Alzheimer’s disease and predictor of Aβ burden through induction of APP amyloidogenic processing. Mol. Psychiatry, 2021, 26(10), 5516-5531.
[http://dx.doi.org/10.1038/s41380-021-01248-1] [PMID: 34400772]
[10]
van Bergen, J.M.G.; Li, X.; Hua, J.; Schreiner, S.J.; Steininger, S.C.; Quevenco, F.C.; Wyss, M.; Gietl, A.F.; Treyer, V.; Leh, S.E.; Buck, F.; Nitsch, R.M.; Pruessmann, K.P.; van Zijl, P.C.M.; Hock, C.; Unschuld, P.G. Colocalization of cerebral iron with amyloid beta in mild cognitive impairment. Sci. Rep., 2016, 6, 35514.
[http://dx.doi.org/10.1038/srep35514] [PMID: 27748454]
[11]
Rodrigue, K.M.; Haacke, E.M.; Raz, N. Differential effects of age and history of hypertension on regional brain volumes and iron. Neuroimage, 2011, 54(2), 750-759.
[http://dx.doi.org/10.1016/j.neuroimage.2010.09.068] [PMID: 20923707]
[12]
Callaghan, M.F.; Freund, P.; Draganski, B.; Anderson, E.; Cappelletti, M.; Chowdhury, R.; Diedrichsen, J.; Fitzgerald, T.H.B.; Smittenaar, P.; Helms, G.; Lutti, A.; Weiskopf, N. Widespread age-related differences in the human brain microstructure revealed by quantitative magnetic resonance imaging. Neurobiol. Aging, 2014, 35(8), 1862-1872.
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.02.008] [PMID: 24656835]
[13]
Collingwood, J.F.; Davidson, M.R. The role of iron in neurodegenerative disorders: Insights and opportunities with synchrotron light. Front. Pharmacol., 2014, 5, 191.
[http://dx.doi.org/10.3389/fphar.2014.00191] [PMID: 25191270]
[14]
Guerreiro, C.; Silva, B.; Crespo, Â.C.; Marques, L.; Costa, S.; Timóteo, Â.; Marcelino, E.; Maruta, C.; Vilares, A.; Matos, M.; Couto, F.S.; Faustino, P.; Verdelho, A.; Guerreiro, M.; Herrero, A.; Costa, C.; de Mendonça, A.; Martins, M.; Costa, L. Decrease in APP and CP mRNA expression supports impairment of iron export in Alzheimer’s disease patients. Biochim. Biophys. Acta, 2015, 1852(10 Pt A), 2116-2122.
[http://dx.doi.org/10.1016/j.bbadis.2015.07.017] [PMID: 26209012]
[15]
Cahill, C.M.; Lahiri, D.K.; Huang, X.; Rogers, J.T. Amyloid precursor protein and alpha synuclein translation, implications for iron and inflammation in neurodegenerative diseases. Biochim. Biophys. Acta, 2009, 1790(7), 615-628.
[http://dx.doi.org/10.1016/j.bbagen.2008.12.001] [PMID: 19166904]
[16]
Cho, H.H.; Cahill, C.M.; Vanderburg, C.R.; Scherzer, C.R.; Wang, B.; Huang, X.; Rogers, J.T. Selective translational control of the Alzheimer amyloid precursor protein transcript by iron regulatory protein-1. J. Biol. Chem., 2010, 285(41), 31217-31232.
[http://dx.doi.org/10.1074/jbc.M110.149161] [PMID: 20558735]
[17]
Bandyopadhyay, S.; Huang, X.; Cho, H.; Greig, N.H.; Youdim, M.B.; Rogers, J.T. 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), 237-247.
[http://dx.doi.org/10.1007/978-3-211-33328-0_25] [PMID: 17447434]
[18]
Smith, M.A.; Harris, P.L.R.; Sayre, L.M.; Perry, G. Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc. Natl. Acad. Sci. USA, 1997, 94(18), 9866-9868.
[http://dx.doi.org/10.1073/pnas.94.18.9866] [PMID: 9275217]
[19]
Peters, D.G.; Pollack, A.N.; Cheng, K.C.; Sun, D.; Saido, T.; Haaf, M.P.; Yang, Q.X.; Connor, J.R.; Meadowcroft, M.D. Dietary lipophilic iron alters amyloidogenesis and microglial morphology in Alzheimer’s disease knock-in APP mice. Metallomics, 2018, 10(3), 426-443.
[http://dx.doi.org/10.1039/C8MT00004B] [PMID: 29424844]
[20]
Plascencia-Villa, G.; Ponce, A.; Collingwood, J.F.; Arellano-Jiménez, M.J.; Zhu, X.; Rogers, J.T.; Betancourt, I.; José-Yacamán, M.; Perry, G. High-resolution analytical imaging and electron holography of magnetite particles in amyloid cores of Alzheimer’s disease. Sci. Rep., 2016, 6, 24873.
[http://dx.doi.org/10.1038/srep24873] [PMID: 27121137]
[21]
Everett, J.; Collingwood, J.F.; Tjendana-Tjhin, V.; Brooks, J.; Lermyte, F.; Plascencia-Villa, G.; Hands-Portman, I.; Dobson, J.; Perry, G.; Telling, N.D. Nanoscale synchrotron X-ray speciation of iron and calcium compounds in amyloid plaque cores from Alzheimer’s disease subjects. Nanoscale, 2018, 10(25), 11782-11796.
[http://dx.doi.org/10.1039/C7NR06794A] [PMID: 29688240]
[22]
Ayton, S.; James, S.A.; Bush, A.I. Nanoscale Imaging Reveals Big Role for Iron in Alzheimer’s Disease. Cell Chem. Biol., 2017, 24(10), 1192-1194.
[http://dx.doi.org/10.1016/j.chembiol.2017.10.002] [PMID: 29053948]
[23]
Telling, N.D.; Everett, J.; Collingwood, J.F.; Dobson, J.; van der Laan, G.; Gallagher, J.J.; Wang, J.; Hitchcock, A.P. Iron biochemistry is correlated with amyloid plaque morphology in an established mouse model of Alzheimer’s disease. Cell Chem. Biol., 2017, 24(10), 1205-1215.e3.
[http://dx.doi.org/10.1016/j.chembiol.2017.07.014] [PMID: 28890316]
[24]
Boopathi, S.; Kolandaivel, P. Fe2+ binding on amyloid β-peptide promotes aggregation. Proteins, 2016, 84(9), 1257-1274.
[http://dx.doi.org/10.1002/prot.25075] [PMID: 27214008]
[25]
Tahirbegi, I.B.; Pardo, W.A.; Alvira, M.; Mir, M.; Samitier, J. Amyloid Aβ 42, a promoter of magnetite nanoparticle formation in Alzheimer's disease. Nanotechnology, 2016, 27(46), 465102.
[http://dx.doi.org/10.1088/0957-4484/27/46/465102] [PMID: 27734811]
[26]
Bodovitz, S.; Falduto, M.T.; Frail, D.E.; Klein, W.L. Iron levels modulate alpha-secretase cleavage of amyloid precursor protein. J. Neurochem., 1995, 64(1), 307-315.
[http://dx.doi.org/10.1046/j.1471-4159.1995.64010307.x] [PMID: 7798927]
[27]
Silvestri, L.; Camaschella, C. A potential pathogenetic role of iron in Alzheimer’s disease. J. Cell. Mol. Med., 2008, 12(5A), 1548-1550.
[http://dx.doi.org/10.1111/j.1582-4934.2008.00356.x] [PMID: 18466351]
[28]
Ward, R.J.; Zucca, F.A.; Duyn, J.H.; Crichton, R.R.; Zecca, L. The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol., 2014, 13(10), 1045-1060.
[http://dx.doi.org/10.1016/S1474-4422(14)70117-6] [PMID: 25231526]
[29]
Li, X.; Liu, Y.; Zheng, Q.; Yao, G.; Cheng, P.; Bu, G.; Xu, H.; Zhang, Y.W. Ferritin light chain interacts with PEN-2 and affects γ-secretase activity. Neurosci. Lett., 2013, 548, 90-94.
[http://dx.doi.org/10.1016/j.neulet.2013.05.018] [PMID: 23685131]
[30]
Everett, J.; Brooks, J.; Lermyte, F.; O’Connor, P.B.; Sadler, P.J.; Dobson, J.; Collingwood, J.F.; Telling, N.D. Iron stored in ferritin is chemically reduced in the presence of aggregating Aβ(1-42). Sci. Rep., 2020, 10, 1-10332.
[http://dx.doi.org/10.1038/s41598-020-67117-z] [PMID: 32587293]
[31]
Tahmasebinia, F.; Emadi, S. Effect of metal chelators on the aggregation of beta-amyloid peptides in the presence of copper and iron. Biometals, 2017, 30(2), 285-293.
[http://dx.doi.org/10.1007/s10534-017-0005-2] [PMID: 28281098]
[32]
Galante, D.; Cavallo, E.; Perico, A.; D’Arrigo, C. Effect of ferric citrate on amyloid-beta peptides behavior. Biopolymers, 2018, 109(6), e23224.
[http://dx.doi.org/10.1002/bip.23224] [PMID: 29897618]
[33]
Ha, C.; Ryu, J.; Park, C.B. Metal ions differentially influence the aggregation and deposition of Alzheimer’s β-amyloid on a solid template. Biochemistry, 2007, 46(20), 6118-6125.
[http://dx.doi.org/10.1021/bi7000032] [PMID: 17455909]
[34]
Dahms, S.O.; Könnig, I.; Roeser, D.; Gührs, K.H.; Mayer, M.C.; Kaden, D.; Multhaup, G.; Than, M.E. Metal binding dictates conformation and function of the amyloid precursor protein (APP) E2 domain. J. Mol. Biol., 2012, 416(3), 438-452.
[http://dx.doi.org/10.1016/j.jmb.2011.12.057] [PMID: 22245578]
[35]
Cohen, S.I.A.; Linse, S.; Luheshi, L.M.; Hellstrand, E.; White, D.A.; Rajah, L.; Otzen, D.E.; Vendruscolo, M.; Dobson, C.M.; Knowles, T.P.J. Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism. Proc. Natl. Acad. Sci. USA, 2013, 110(24), 9758-9763.
[http://dx.doi.org/10.1073/pnas.1218402110] [PMID: 23703910]
[36]
Balejcikova, L.; Siposova, K.; Kopcansky, P.; Safarik, I. Fe(II) formation after interaction of the amyloid β-peptide with iron-storage protein ferritin. J. Biol. Phys., 2018, 44(3), 237-243.
[http://dx.doi.org/10.1007/s10867-018-9498-3] [PMID: 29740739]
[37]
Everett, J.; Céspedes, E.; Shelford, L.R.; Exley, C.; Collingwood, J.F.; Dobson, J.; van der Laan, G.; Jenkins, C.A.; Arenholz, E.; Telling, N.D. Ferrous iron formation following the co-aggregation of ferric iron and the Alzheimer’s disease peptide β-amyloid (1-42). J. R. Soc. Interface, 2014, 11(95), 20140165.
[http://dx.doi.org/10.1098/rsif.2014.0165] [PMID: 24671940]
[38]
Mena, N.P.; Urrutia, P.J.; Lourido, F.; Carrasco, C.M.; Núñez, M.T. Mitochondrial iron homeostasis and its dysfunctions in neurodegenerative disorders. Mitochondrion, 2015, 21, 92-105.
[http://dx.doi.org/10.1016/j.mito.2015.02.001] [PMID: 25667951]
[39]
Banerjee, P.; Sahoo, A.; Anand, S.; Ganguly, A.; Righi, G.; Bovicelli, P.; Saso, L.; Chakrabarti, S. Multiple mechanisms of iron-induced amyloid beta-peptide accumulation in SHSY5Y cells: Protective action of negletein. Neuromolecular Med., 2014, 16(4), 787-798.
[http://dx.doi.org/10.1007/s12017-014-8328-4] [PMID: 25249289]
[40]
Chen, Y.T.; Chen, W.Y.; Huang, X.T.; Xu, Y.C.; Zhang, H.Y. Iron dysregulates APP processing accompanying with sAPPα cellular retention and β-secretase inhibition in rat cortical neurons. Acta Pharmacol. Sin., 2018, 39(2), 177-183.
[http://dx.doi.org/10.1038/aps.2017.113] [PMID: 28836584]
[41]
Lane, D.J.R.; Ayton, S.; Bush, A.I. Iron and Alzheimer’s disease: an update on emerging mechanisms. J. Alzheimers Dis., 2018, 64(s1), S379-S395.
[http://dx.doi.org/10.3233/JAD-179944] [PMID: 29865061]
[42]
Everett, J.; Lermyte, F.; Brooks, J.; Tjendana-Tjhin, V.; Plascencia-Villa, G.; Hands-Portman, I.; Donnelly, J.M.; Billimoria, K.; Perry, G.; Zhu, X.; Sadler, P.J.; O’Connor, P.B.; Collingwood, J.F.; Telling, N.D. Biogenic metallic elements in the human brain? Sci. Adv., 2021, 7(24), 7.
[http://dx.doi.org/10.1126/sciadv.abf6707] [PMID: 34108207]
[43]
Amit, T.; Avramovich-Tirosh, Y.; Youdim, M.B.H.; Mandel, S. Targeting multiple Alzheimer’s disease etiologies with multimodal neuroprotective and neurorestorative iron chelators. FASEB J., 2008, 22(5), 1296-1305.
[http://dx.doi.org/10.1096/fj.07-8627rev] [PMID: 18048580]
[44]
Yamamoto, A.; Shin, R-W.; Hasegawa, K.; Naiki, H.; Sato, H.; Yoshimasu, F.; Kitamoto, T. Iron (III) induces aggregation of hyperphosphorylated τ and its reduction to iron (II) reverses the aggregation: Implications in the formation of neurofibrillary tangles of Alzheimer’s disease. J. Neurochem., 2002, 82(5), 1137-1147.
[http://dx.doi.org/10.1046/j.1471-4159.2002.t01-1-01061.x] [PMID: 12358761]
[45]
Lei, P.; Ayton, S.; Finkelstein, D.I.; Spoerri, L.; Ciccotosto, G.D.; Wright, D.K.; Wong, B.X.W.; Adlard, P.A.; Cherny, R.A.; Lam, L.Q.; Roberts, B.R.; Volitakis, I.; Egan, G.F.; McLean, C.A.; Cappai, R.; Duce, J.A.; Bush, A.I. Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export. Nat. Med., 2012, 18(2), 291-295.
[http://dx.doi.org/10.1038/nm.2613] [PMID: 22286308]
[46]
Xie, L.; Zheng, W.; Xin, N.; Xie, J.W.; Wang, T.; Wang, Z.Y. Ebselen inhibits iron-induced tau phosphorylation by attenuating DMT1 up-regulation and cellular iron uptake. Neurochem. Int., 2012, 61(3), 334-340.
[http://dx.doi.org/10.1016/j.neuint.2012.05.016] [PMID: 22634399]
[47]
Guo, C.; Wang, P.; Zhong, M.L.; Wang, T.; Huang, X.S.; Li, J.Y.; Wang, Z.Y. Deferoxamine inhibits iron induced hippocampal tau phosphorylation in the Alzheimer transgenic mouse brain. Neurochem. Int., 2013, 62(2), 165-172.
[http://dx.doi.org/10.1016/j.neuint.2012.12.005] [PMID: 23262393]
[48]
Reynolds, M.R.; Reyes, J.F.; Fu, Y.; Bigio, E.H.; Guillozet-Bongaarts, A.L.; Berry, R.W.; Binder, L.I. Tau nitration occurs at tyrosine 29 in the fibrillar lesions of Alzheimer’s disease and other tauopathies. J. Neurosci., 2006, 26(42), 10636-10645.
[http://dx.doi.org/10.1523/JNEUROSCI.2143-06.2006] [PMID: 17050703]
[49]
Kummer, M.P.; Hermes, M.; Delekarte, A.; Hammerschmidt, T.; Kumar, S.; Terwel, D.; Walter, J.; Pape, H.C.; König, S.; Roeber, S.; Jessen, F.; Klockgether, T.; Korte, M.; Heneka, M.T. Nitration of tyrosine 10 critically enhances amyloid β aggregation and plaque formation. Neuron, 2011, 71(5), 833-844.
[http://dx.doi.org/10.1016/j.neuron.2011.07.001] [PMID: 21903077]
[50]
Wang, D.; Hui, Y.; Peng, Y.; Tang, L.; Jin, J.; He, R.; Li, Y.; Zhang, S.; Li, L.; Zhou, Y.; Li, J.; Ma, N.; Li, J.; Li, S.; Gao, X.; Luo, S. Overexpression of heme oxygenase 1 causes cognitive decline and affects pathways for tauopathy in mice. J. Alzheimers Dis., 2015, 43(2), 519-534.
[http://dx.doi.org/10.3233/JAD-140567] [PMID: 25114080]
[51]
Damulina, A.; Pirpamer, L.; Soellradl, M.; Sackl, M.; Tinauer, C.; Hofer, E.; Enzinger, C.; Gesierich, B.; Duering, M.; Ropele, S.; Schmidt, R.; Langkammer, C. Cross-sectional and longitudinal assessment of brain iron level in Alzheimer disease using 3-T MRI. Radiology, 2020, 296(3), 619-626.
[http://dx.doi.org/10.1148/radiol.2020192541] [PMID: 32602825]

© 2024 Bentham Science Publishers | Privacy Policy