{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:10:29Z","timestamp":1787238629668,"version":"build-2736575974"},"reference-count":152,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T00:00:00Z","timestamp":1733875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018990","name":"Alfaisal University, Riyadh, Saudi Arabia","doi-asserted-by":"publisher","award":["IRG20413"],"award-info":[{"award-number":["IRG20413"]}],"id":[{"id":"10.13039\/501100018990","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The hallmark of Alzheimer\u2019s disease (AD) is the buildup of amyloid-\u03b2 (A\u03b2), which is produced when the amyloid precursor protein (APP) misfolds and deposits as neurotoxic plaques in the brain. A functional iron responsive element (IRE) RNA stem loop is encoded by the APP 5\u2032-UTR and may be a target for regulating the production of Alzheimer\u2019s amyloid precursor protein. Since modifying A\u03b2 protein expression can give anti-amyloid efficacy and protective brain iron balance, targeted regulation of amyloid protein synthesis through modulation of 5\u2032-UTR sequence function is a novel method for the prospective therapy of Alzheimer\u2019s disease. Numerous mRNA interference strategies target the 2D RNA structure, even though messenger RNAs like tRNAs and rRNAs can fold into complex, three-dimensional structures, adding even another level of complexity. The IRE family is among the few known 3D mRNA regulatory elements. This review seeks to describe the structural and functional aspects of IREs in transcripts, including that of the amyloid precursor protein, that are relevant to neurodegenerative diseases, including AD. The mRNAs encoding the proteins involved in iron metabolism are controlled by this family of similar base sequences. Like ferritin IRE RNA in their 5\u2032-UTR, iron controls the production of APP in their 5\u2032-UTR. Iron misregulation by iron regulatory proteins (IRPs) can also be investigated and contrasted using measurements of the expression levels of tau production, A\u03b2, and APP. The development of AD is aided by iron binding to A\u03b2, which promotes A\u03b2 aggregation. The development of small chemical therapeutics to control IRE-modulated expression of APP is increasingly thought to target messenger RNAs. Thus, IRE-modulated APP expression in AD has important therapeutic implications by targeting mRNA structures.<\/jats:p>","DOI":"10.3390\/ph17121669","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T03:14:58Z","timestamp":1733886898000},"page":"1669","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Targeting Iron Responsive Elements (IREs) of APP mRNA into Novel Therapeutics to Control the Translation of Amyloid-\u03b2 Precursor Protein in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2300-4595","authenticated-orcid":false,"given":"Mateen A.","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Life Science, College of Science and General Studies, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/aps.2017.28","article-title":"Amyloid beta: Structure, biology and structure-based therapeutic development","volume":"38","author":"Chen","year":"2017","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.tibs.2023.10.005","article-title":"Cryo-EM structures of functional and pathological amyloid ribonucleoprotein assemblies","volume":"49","author":"Ventura","year":"2024","journal-title":"Trends Biochem. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.str.2022.05.002","article-title":"Thermodynamic analysis of amyloid fibril structures reveals a common framework for stability in amyloid polymorphs","volume":"30","author":"Louros","year":"2022","journal-title":"Structure"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"14193","DOI":"10.1073\/pnas.2332851100","article-title":"In Vivo reduction of amyloid-\u03b2 by a mutant copper transporter","volume":"100","author":"Phinney","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13024-023-00654-z","article-title":"Amyloid fibril proteomics of AD brains reveals modifiers of aggregation and toxicity","volume":"18","author":"Upadhyay","year":"2023","journal-title":"Mol. Neurodegener."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/scientificamerican0506-72","article-title":"Shutting down Alzheimer\u2019s","volume":"294","author":"Wolfe","year":"2006","journal-title":"Sci. Am."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/jnc.14834","article-title":"Transferrin and H-ferritin involvement in brain iron acquisition during postnatal development: Impact of sex and genotype","volume":"152","author":"Chiou","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e2527","DOI":"10.1002\/brb3.2527","article-title":"Effect of metal ions on Alzheimer\u2019s disease","volume":"12","author":"Liu","year":"2022","journal-title":"Brain Behav."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/416535a","article-title":"Naturally secreted oligomers of amyloid \u03b2 protein potently inhibit hippocampal long-term potentiation in vivo","volume":"416","author":"Walsh","year":"2002","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.tins.2004.01.007","article-title":"More than just two peas in a pod: Common amyloidogenic properties of tau and \u03b1-synuclein in neurodegenerative diseases","volume":"27","author":"Lee","year":"2004","journal-title":"Trends Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Olufunmilayo, E.O., and Holsinger, R.M.D. (2023). Roles of Non-Coding RNA in Alzheimer\u2019s Disease Pathophysiology. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512498"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1007\/s12035-020-02277-7","article-title":"New Insights into the Role of Ferritin in Iron Homeostasis and Neurodegenerative Diseases","volume":"58","author":"Zhang","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1056\/NEJMra1004967","article-title":"Iron overload in human disease","volume":"366","author":"Fleming","year":"2012","journal-title":"New Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S1471-4914(00)01910-9","article-title":"Brain iron transport and neurodegeneration","volume":"7","author":"Qian","year":"2001","journal-title":"Trends Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/S1474-4422(03)00353-3","article-title":"Iron misregulation in the brain: A primary cause of neurodegenerative disorders","volume":"2","author":"Ke","year":"2003","journal-title":"Lancet Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/jnc.15954","article-title":"Amyloid-\u03b2 exposed astrocytes induce iron transport from endothelial cells at the blood\u2013brain barrier by altering the ratio of apo- and holo-transferrin","volume":"167","author":"Baringer","year":"2023","journal-title":"J. Neurochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1111\/jnc.15819","article-title":"Brain iron acquisition: An overview of homeostatic regulation and disease dysregulation","volume":"165","author":"Baringer","year":"2023","journal-title":"J. Neurochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.3233\/JAD-170662","article-title":"Metals and Alzheimer\u2019s Disease: How Far Have We Come in the Clinic?","volume":"62","author":"Paul","year":"2018","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/978-981-13-9589-5_4","article-title":"Iron Pathophysiology in Parkinson Diseases","volume":"1173","author":"Jiang","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Dusek, P., Hofer, T., Alexander, J., Roos, P.M., and Aaseth, J.O. (2022). Cerebral Iron Deposition in Neurodegeneration. Biomolecules, 12.","DOI":"10.3390\/biom12050714"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wong, B.X., Tsatsanis, A., Lim, L.Q., Adlard, P.A., Bush, A.I., and Duce, J.A. (2014). \u03b2-Amyloid precursor protein does not possess ferroxidase activity but does stabilize the cell surface ferrous iron exporter ferroportin. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0114174"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s13024-017-0218-4","article-title":"Iron regulatory protein (IRP)-iron responsive element (IRE) signaling pathway in human neurodegenerative diseases","volume":"12","author":"Zhou","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S277","DOI":"10.3233\/JAD-2012-129011","article-title":"The metal theory of Alzheimer\u2019s disease","volume":"33","author":"Bush","year":"2013","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wilkinson, N., and Pantopoulos, K. (2014). The IRP\/IRE system in vivo: Insights from mouse models. Front. Pharmacol., 5.","DOI":"10.3389\/fphar.2014.00176"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zhang, D.L., Ghosh, M.C., and Rouault, T.A. (2014). The physiological functions of iron regulatory proteins in iron homeostasis\u2014An update. Front. Pharmacol., 5.","DOI":"10.3389\/fphar.2014.00124"},{"key":"ref_27","first-page":"761","article-title":"Alterations in the interaction between iron regulatory proteins and their iron responsive element in normal and Alzheimer\u2019s diseased brains","volume":"46","author":"Pinero","year":"2000","journal-title":"Cell Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"45518","DOI":"10.1074\/jbc.M207435200","article-title":"An Iron-responsive Element Type II in the 5\u2032-Untranslated Region of the Alzheimer\u2019s Amyloid Precursor Protein Transcript","volume":"277","author":"Rogers","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/978-3-211-33328-0_25","article-title":"Metal specificity of an iron-responsive element in Alzheimer\u2019s APP mRNA 5\u2032untranslated region, tolerance of SH-SY5Y and H4 neural cells to desferrioxamine, clioquinol, VK-28, and a piperazine chelator","volume":"71","author":"Bandyopadhyay","year":"2006","journal-title":"J. Neural Transm. Suppl."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1261\/rna.464807","article-title":"Evolution of the iron-responsive element","volume":"13","author":"Piccinelli","year":"2007","journal-title":"RNA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1196\/annals.1306.001","article-title":"Iron metabolism and the IRE\/IRP regulatory system: An update","volume":"1012","author":"Pantopoulos","year":"2004","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"31217","DOI":"10.1074\/jbc.M110.149161","article-title":"Selective translational control of the Alzheimer amyloid precursor protein transcript by iron regulatory protein-1","volume":"285","author":"Cho","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1042\/BJ20101825","article-title":"Regulation of cellular iron metabolism","volume":"434","author":"Wang","year":"2012","journal-title":"Biochem. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0092-8674(04)00343-5","article-title":"Balancing acts: Molecular control of mammalian iron metabolism","volume":"117","author":"Hentze","year":"2004","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1107\/S1744309106004192","article-title":"Crystallization and preliminary X-ray diffraction analysis of iron regulatory protein 1 in complex with ferritin IRE RNA","volume":"62","author":"Selezneva","year":"2006","journal-title":"Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"11995","DOI":"10.1074\/jbc.M110938200","article-title":"Structural changes associated with switching activities of human iron regulatory protein 1","volume":"277","author":"Brazzolotto","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5138","DOI":"10.1038\/sj.emboj.7601380","article-title":"Cap-free structure of eIF4E suggests a basis for conformational regulation by its ligands","volume":"25","author":"Volpon","year":"2006","journal-title":"EMBO J."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Khan, M.A., Malik, A., Domashevskiy, A.V., San, A., and Khan, J.A. (2020). Interaction of ferritin iron responsive element (IRE) mRNA with translation initiation factor eIF4F. Spectrochim. Acta Part A Mol. Biomol. Spectrosc., 243.","DOI":"10.1016\/j.saa.2020.118776"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Khan, M.A., Walden, W.E., Theil, E.C., and Goss, D.J. (2017). Thermodynamic and kinetic analyses of iron response element (IRE)-mRNA binding to iron regulatory protein, IRP1. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-09093-5"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Khan, M.A., Mohammad, T., Malik, A., Hassan, M.I., and Domashevskiy, A.V. (2023). Iron response elements (IREs)-mRNA of Alzheimer\u2019s amyloid precursor protein binding to iron regulatory protein (IRP1): A combined molecular docking and spectroscopic approach. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-32073-x"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"30122","DOI":"10.1074\/jbc.M109.041061","article-title":"Direct Fe2+ sensing by iron-responsive messenger RNA: Repressor complexes weakens binding","volume":"284","author":"Khan","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Khan, M.A., Yumak, S., and Miyoshi, H. (2024). Poly(A)-binding protein promotes VPg-dependent translation of potyvirus through enhanced binding of phosphorylated eIFiso4F and eIFiso4F\u2219eIF4B. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0300287"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1073\/pnas.1905057117","article-title":"Translation of the intrinsically disordered protein \u03b1-synuclein is inhibited by a small molecule targeting its structured mRNA","volume":"117","author":"Zhang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hare, D., Ayton, S., Bush, A., and Lei, P. (2013). A delicate balance: Iron metabolism and diseases of the brain. Front. Aging Neurosci., 5.","DOI":"10.3389\/fnagi.2013.00034"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1046\/j.1471-4159.2003.02142.x","article-title":"The significance of the mutated divalent metal transporter (DMT1) on iron transport into the Belgrade rat brain","volume":"88","author":"Moos","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Ashraf, A., Clark, M., and So, P.-W. (2018). The Aging of Iron Man. Front. Aging Neurosci., 10.","DOI":"10.3389\/fnagi.2018.00065"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/j.bbadis.2013.04.007","article-title":"Iron uptake in quiescent and inflammation-activated astrocytes: A potentially neuroprotective control of iron burden","volume":"1832","author":"Pelizzoni","year":"2013","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.spen.2006.08.002","article-title":"Brain iron metabolism","volume":"13","author":"Rouault","year":"2006","journal-title":"Semin. Pediatr. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1016\/j.biocel.2004.02.007","article-title":"Transferrin receptor 1","volume":"36","author":"Aisen","year":"2004","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/nrm2295","article-title":"Regulation of iron acquisition and storage: Consequences for iron-linked disorders","volume":"9","author":"Kaplan","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ingrassia, R., Garavaglia, B., and Memo, M. (2019). DMT1 Expression and Iron Levels at the Crossroads Between Aging and Neurodegeneration. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00575"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Rosenblum, S.L., and Kosman, D.J. (2022). Aberrant Cerebral Iron Trafficking Co-morbid With Chronic Inflammation: Molecular Mechanisms and Pharmacologic Intervention. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.855751"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/jnc.13425","article-title":"Iron neurochemistry in Alzheimer\u2019s disease and Parkinson\u2019s disease: Targets for therapeutics","volume":"139","author":"Belaidi","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.cmet.2005.02.005","article-title":"Cellular iron: Ferroportin is the only way out","volume":"1","author":"Ganz","year":"2005","journal-title":"Cell Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1146\/annurev.neuro.30.051606.094232","article-title":"Copper and iron disorders of the brain","volume":"30","author":"Madsen","year":"2007","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1038\/nrn1537","article-title":"Iron, brain ageing and neurodegenerative disorders","volume":"5","author":"Zecca","year":"2004","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/1097-0029(20010101)52:1<89::AID-JEMT11>3.0.CO;2-2","article-title":"Toxicology of choroid plexus: Special reference to metal-induced neurotoxicities","volume":"52","author":"Zheng","year":"2001","journal-title":"Microsc. Res. Tech."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0041-008X(03)00251-5","article-title":"Brain barrier systems: A new frontier in metal neurotoxicological research","volume":"192","author":"Zheng","year":"2003","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"109137","DOI":"10.1016\/j.envres.2020.109137","article-title":"Alzheimer disease starts in childhood in polluted Metropolitan Mexico City. A major health crisis in progress","volume":"183","author":"Kulesza","year":"2020","journal-title":"Environ. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1038\/s41593-018-0221-2","article-title":"Selective vulnerability in neurodegenerative diseases","volume":"21","author":"Fu","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1111\/nan.12387","article-title":"Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: The pathological building blocks of early Alzheimer\u2019s disease","volume":"43","author":"Ehrenberg","year":"2017","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0891-0618(98)00061-1","article-title":"What are the facts and artifacts of the pathogenesis and etiology of Alzheimer disease?","volume":"16","author":"Smith","year":"1998","journal-title":"J. Chem. Neuroanat."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jtemb.2016.06.005","article-title":"Nucleic acid oxidative damage in Alzheimer\u2019s disease\u2014explained by the hepcidin-ferroportin neuronal iron overload hypothesis?","volume":"38","author":"Hofer","year":"2016","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Ma, L., Azad, M.G., Dharmasivam, M., Richardson, V., Quinn, R.J., Feng, Y., Pountney, D.L., Tonissen, K.F., Mellick, G.D., and Yanatori, I. (2021). Parkinson\u2019s disease: Alterations in iron and redox biology as a key to unlock therapeutic strategies. Redox Biol., 41.","DOI":"10.1016\/j.redox.2021.101896"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Urrutia, P.J., B\u00f3rquez, D.A., and N\u00fa\u00f1ez, M.T. (2021). Inflaming the Brain with Iron. Antioxidants, 10.","DOI":"10.3390\/antiox10010061"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Hinarejos, I., Machuca-Arellano, C., Sancho, P., and Carmen Espin\u00f3s, C. (2020). Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA). Review Antioxidants, 9.","DOI":"10.3390\/antiox9101020"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1212\/01.wnl.0000259542.54830.34","article-title":"Brain structural alterations before mild cognitive impairment","volume":"68","author":"Smith","year":"2007","journal-title":"Neurology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4248","DOI":"10.1074\/jbc.M110.158980","article-title":"Iron promotes the toxicity of amyloid beta peptide by impeding its ordered aggregation","volume":"286","author":"Liu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.freeradbiomed.2020.03.015","article-title":"Ferroptosis was more initial in cell death caused by iron overload and its underlying mechanism in Parkinson\u2019s disease","volume":"152","author":"Zhang","year":"2020","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Abdalkader, M., Lampinen, R., Kanninen, K.M., Malm, T.M., and Liddell, J.R. (2018). Targeting Nrf2 to Suppress Ferroptosis and Mitochondrial Dysfunction in Neurodegeneration. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00466"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease","volume":"171","author":"Stockwell","year":"2017","journal-title":"Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1101\/lm.052282.120","article-title":"Iron-responsive-like elements and neurodegenerative ferroptosis","volume":"27","author":"Rogers","year":"2020","journal-title":"Learn. Mem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.gene.2019.06.012","article-title":"Relevance of the iron-responsive element (IRE) pseudotriloop structure for IRP1\/2 binding and validation of IRE-like structures using the yeast three-hybrid system","volume":"710","author":"Chen","year":"2019","journal-title":"Gene"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e933084","DOI":"10.12659\/MSM.933084","article-title":"The Role of Amyloid-Beta and Tau in the Early Pathogenesis of Alzheimer\u2019s Disease","volume":"27","author":"Yin","year":"2021","journal-title":"Med. Sci. Monit."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.3233\/JAD-220002","article-title":"The Associations of Cerebrospinal Fluid Ferritin with Neurodegeneration and Neuroinflammation Along the Alzheimer\u2019s Disease Continuum","volume":"88","author":"Pan","year":"2022","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2932","DOI":"10.1038\/s41380-019-0375-7","article-title":"Brain iron is associated with accelerated cognitive decline in people with Alzheimer pathology","volume":"25","author":"Ayton","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.bcp.2014.01.032","article-title":"Alzheimer\u2019s disease therapeutics targeted to the control of amyloid precursor protein translation: Maintenance of brain iron homeostasis","volume":"88","author":"Bandyopadhyay","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Peng, Y., Chang, X., and Lang, M. (2021). Iron Homeostasis Disorder and Alzheimer\u2019s Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212442"},{"key":"ref_79","first-page":"e12002","article-title":"APOE4 moderates effects of cortical iron on synchronized default mode network activity in cognitively healthy old-aged adults","volume":"12","author":"Kagerer","year":"2020","journal-title":"Alzheimers Dement. Diagn. Assess. Dis. Monit."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1007\/s13311-018-0656-x","article-title":"Marked Age-Related Changes in Brain Iron Homeostasis in Amyloid Protein Precursor Knockout Mice","volume":"15","author":"Belaidi","year":"2018","journal-title":"Neurotherapeutics"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Wan, W., Cao, L., Kalionis, B., Murthi, P., Xia, S., and Guan, Y. (2019). Iron Deposition Leads to Hyperphosphorylation of Tau and Disruption of Insulin Signaling. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00607"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"LeVine, S.M. (2024). Exploring Potential Mechanisms Accounting for Iron Accumulation in the Central Nervous System of Patients with Alzheimer\u2019s Disease. Cells, 13.","DOI":"10.3390\/cells13080689"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"LeVine, S.M., and Tsau, S.S.G. (2023). Exploring Whether Iron Sequestration within the CNS of Patients with Alzheimer\u2019s Disease Causes a Functional Iron Deficiency That Advances Neurodegeneration. Brain Sci., 13.","DOI":"10.3390\/brainsci13030511"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.mod.2012.11.001","article-title":"Roles of the amyloid precursor protein family in the peripheral nervous system","volume":"130","author":"Caldwell","year":"2013","journal-title":"Mech. Dev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"523","DOI":"10.3233\/JAD-2012-111169","article-title":"Overexpression of human wild-type amyloid-\u03b2 protein precursor decreases the iron content and increases the oxidative stress of neuroblastoma SH-SY5Y cells","volume":"30","author":"Wan","year":"2012","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"809","DOI":"10.15252\/embr.201338064","article-title":"sAPP modulates iron efflux from brain microvascular endothelial cells by stabilizing the ferrous iron exporter ferroportin","volume":"15","author":"McCarthy","year":"2014","journal-title":"Embo Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.bbagen.2008.12.001","article-title":"Amyloid precursor protein and alpha synuclein translation, implications for iron and inflammation in neurodegenerative diseases","volume":"1790","author":"Cahill","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Lei, P., Ayton, S., and Bush, A.I. (2021). The essential elements of Alzheimer\u2019s disease. J. Biol. Chem., 296.","DOI":"10.1074\/jbc.REV120.008207"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.3233\/JAD-210200","article-title":"Iron Responsive Element-Mediated Responses to Iron Dyshomeostasis in Alzheimer\u2019s Disease","volume":"84","author":"Hin","year":"2021","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5541","DOI":"10.2147\/IJN.S200490","article-title":"Alzheimer\u2019s disease: Pathogenesis, diagnostics, and therapeutics","volume":"14","author":"Tiwari","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_91","first-page":"e688","article-title":"Validation of Plasma Amyloid-\u03b2 42\/40 for Detecting Alzheimer Disease Amyloid Plaques","volume":"98","author":"Li","year":"2022","journal-title":"Neurology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"952","DOI":"10.2174\/1567205013666160314150501","article-title":"Molecular Basis of Familial and Sporadic Alzheimer\u2019s Disease","volume":"13","author":"Dorszewska","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.1021\/bi500131a","article-title":"The C-terminal threonine of A\u03b243 nucleates toxic aggregation via structural and dynamical changes in monomers and protofibrils","volume":"53","author":"Conicella","year":"2014","journal-title":"Biochemistry"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/s41392-023-01484-7","article-title":"Amyloid \u03b2-based therapy for Alzheimer\u2019s disease: Challenges, successes and future","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1021\/jz4027612","article-title":"Amyloid Fibrils: Formation, Polymorphism, and Inhibition","volume":"5","year":"2014","journal-title":"J. Phys. Chem. Lett."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"6981","DOI":"10.1021\/bi500695g","article-title":"Mechanism of amyloid-\u03b2 fibril elongation","volume":"53","author":"Gurry","year":"2014","journal-title":"Biochemistry"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"13434","DOI":"10.1039\/C5CC05264E","article-title":"Function and toxicity of amyloid beta and recent therapeutic interventions targeting amyloid beta in Alzheimer\u2019s disease","volume":"51","author":"Rajasekhar","year":"2015","journal-title":"Chem. Commun."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s13195-017-0296-0","article-title":"A coiled conformation of amyloid-beta recognized by antibody C706","volume":"9","author":"Teplyakov","year":"2017","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Tran, L., Basdevant, N., Pr\u00e9vost, C., and Ha-Duong, T. (2016). Structure of ring-shaped A\u03b242 oligomers determined by conformational selection. Sci. Rep., 6.","DOI":"10.1038\/srep21429"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S0896-6273(03)00434-3","article-title":"Triple-transgenic model of Alzheimer\u2019s disease with plaques and tangles: Intracellular Abeta and synaptic dysfunction","volume":"39","author":"Oddo","year":"2003","journal-title":"Neuron"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1126\/science.1079469","article-title":"Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis","volume":"300","author":"Kayed","year":"2003","journal-title":"Science"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"20466","DOI":"10.1074\/jbc.M100175200","article-title":"Alzheimer\u2019s disease amyloid-beta binds copper and zinc to generate an allosterically ordered membrane-penetrating structure containing superoxide dismutase-like subunits","volume":"276","author":"Curtain","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0022-510X(98)00092-6","article-title":"Copper, iron and zinc in Alzheimer\u2019s disease senile plaques","volume":"158","author":"Lovell","year":"1998","journal-title":"J. Neurol. Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1021\/cb400080f","article-title":"Untangling amyloid-\u03b2, tau, and metals in Alzheimer\u2019s disease","volume":"8","author":"Savelieff","year":"2013","journal-title":"ACS Chem. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e76494","DOI":"10.7554\/eLife.76494","article-title":"Assembly of recombinant tau into filaments identical to those of Alzheimer\u2019s disease and chronic traumatic encephalopathy","volume":"11","author":"Koh","year":"2022","journal-title":"eLife"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1073\/pnas.90.5.1977","article-title":"Apolipoprotein E: High-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease","volume":"90","author":"Strittmatter","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Volz, K. (2021). Conservation in the Iron Responsive Element Family. Genes, 12.","DOI":"10.3390\/genes12091365"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1007\/s00018-007-7198-4","article-title":"The family of iron responsive RNA structures regulated by changes in cellular iron and oxygen","volume":"64","author":"Leipuviene","year":"2007","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1146\/annurev.nutr.28.061807.155521","article-title":"Systemic iron homeostasis and the iron-responsive element\/iron-regulatory protein (IRE\/IRP) regulatory network","volume":"28","author":"Muckenthaler","year":"2008","journal-title":"Annu. Rev. Nutr."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.sbi.2007.12.010","article-title":"The functional duality of iron regulatory protein 1","volume":"18","author":"Volz","year":"2008","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"mfac099","DOI":"10.1093\/mtomcs\/mfac099","article-title":"Iron-dependent post transcriptional control of mitochondrial aconitase expression","volume":"15","author":"Shen","year":"2023","journal-title":"Metallomics"},{"key":"ref_112","first-page":"142372","article-title":"The anticholinesterase phenserine and its enantiomer posiphen as 5\u2032untranslated-region-directed translation blockers of the Parkinson\u2019s alpha synuclein expression","volume":"2012","author":"Mikkilineni","year":"2012","journal-title":"Park. Dis."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1261\/rna.1857210","article-title":"Multiple determinants within iron-responsive elements dictate iron regulatory protein binding and regulatory hierarchy","volume":"16","author":"Goforth","year":"2010","journal-title":"RNA"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"4568","DOI":"10.1021\/cr900052g","article-title":"Living with iron (and oxygen): Questions and answers about iron homeostasis","volume":"109","author":"Theil","year":"2009","journal-title":"Chem. Rev."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1126\/science.1133116","article-title":"Structure of dual function iron regulatory protein 1 complexed with ferritin IRE-RNA","volume":"314","author":"Walden","year":"2006","journal-title":"Science"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3740","DOI":"10.1074\/jbc.273.6.3740","article-title":"Iron differentially stimulates translation of mitochondrial aconitase and ferritin mRNAs in mammalian cells. Implications for iron regulatory proteins as regulators of mitochondrial citrate utilization","volume":"273","author":"Schalinske","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"6567","DOI":"10.1093\/nar\/gku248","article-title":"Rapid kinetics of iron responsive element (IRE) RNA\/iron regulatory protein 1 and IRE-RNA\/eIF4F complexes respond differently to metal ions","volume":"42","author":"Khan","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"23637","DOI":"10.1074\/jbc.273.37.23637","article-title":"Loops and bulge\/loops in iron-responsive element isoforms influence iron regulatory protein binding. Fine-tuning of mRNA regulation?","volume":"273","author":"Ke","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1053\/j.seminhematol.2021.06.001","article-title":"Mechanisms of cellular iron sensing, regulation of erythropoiesis and mitochondrial iron utilization","volume":"58","author":"Maio","year":"2021","journal-title":"Semin. Hematol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1111\/jnc.14580","article-title":"Manganese causes neurotoxic iron accumulation via translational repression of amyloid precursor protein and H-Ferritin","volume":"147","author":"Venkataramani","year":"2018","journal-title":"J. Neurochem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.cell.2010.06.028","article-title":"Two to tango: Regulation of Mammalian iron metabolism","volume":"142","author":"Hentze","year":"2010","journal-title":"Cell"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1042\/BST0361282","article-title":"Iron and the translation of the amyloid precursor protein (APP) and ferritin mRNAs: Riboregulation against neural oxidative damage in Alzheimer\u2019s disease","volume":"36","author":"Rogers","year":"2008","journal-title":"Biochem. Soc. Trans."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e168","DOI":"10.1182\/blood-2011-04-343541","article-title":"Iron regulatory protein-1 and -2: Transcriptome-wide definition of binding mRNAs and shaping of the cellular proteome by iron regulatory proteins","volume":"118","author":"Sanchez","year":"2011","journal-title":"Blood"},{"key":"ref_124","first-page":"29","article-title":"Advances in aptamer screening and small molecule aptasensors","volume":"140","author":"Kim","year":"2014","journal-title":"Adv. Biochem. Eng. Biotechnol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.febslet.2011.11.018","article-title":"Accomodating variety in iron-responsive elements: Crystal structure of transferrin receptor 1 B IRE bound to iron regulatory protein 1","volume":"586","author":"Walden","year":"2012","journal-title":"FEBS Lett."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0014-5793(01)03189-1","article-title":"Iron-dependent regulation of the divalent metal ion transporter","volume":"509","author":"Gunshin","year":"2001","journal-title":"FEBS Lett."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.tibs.2010.05.009","article-title":"The REM phase of gene regulation","volume":"35","author":"Hentze","year":"2010","journal-title":"Trends Biochem. Sci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"6235","DOI":"10.1021\/bi9924765","article-title":"Internal loop\/bulge and hairpin loop of the iron-responsive element of ferritin mRNA contribute to maximal iron regulatory protein 2 binding and translational regulation in the iso-iron-responsive element\/iso-iron regulatory protein family","volume":"39","author":"Ke","year":"2000","journal-title":"Biochemistry"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Khan, M.A. (2022). Ferritin iron responsive elements (IREs) mRNA interacts with eIF4G and activates in vitro translation. Front. Biosci., 14.","DOI":"10.31083\/j.fbe1403017"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"88","DOI":"10.2174\/2212796814999200604121937","article-title":"Analysis of ion and pH effects on iron response element (IRE) and mRNA-iroin regulatory protein (IRP1) interactions","volume":"14","author":"Khan","year":"2020","journal-title":"Curr. Chem. Biol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"8417","DOI":"10.1073\/pnas.1120045109","article-title":"Fe2+ binds iron responsive element-RNA, selectively changing protein-binding affinities and regulating mRNA repression and activation","volume":"109","author":"Ma","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"535","DOI":"10.2174\/1389450043345272","article-title":"Metal and inflammatory targets for Alzheimer\u2019s disease","volume":"5","author":"Rogers","year":"2004","journal-title":"Curr. Drug Targets"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.tcb.2013.11.005","article-title":"Maturation of cytosolic and nuclear iron-sulfur proteins","volume":"24","author":"Netz","year":"2014","journal-title":"Trends Cell Biol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1126\/science.1176326","article-title":"An E3 ligase possessing an iron-responsive hemerythrin domain is a regulator of iron homeostasis","volume":"326","author":"Salahudeen","year":"2009","journal-title":"Science"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"12701","DOI":"10.1074\/jbc.M807717200","article-title":"Evidence that phosphorylation of iron regulatory protein 1 at Serine 138 destabilizes the [4Fe-4S] cluster in cytosolic aconitase by enhancing 4Fe-3Fe cycling","volume":"284","author":"Deck","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1002\/hep.27777","article-title":"Iron regulation of hepcidin through Hfe and Hjv: Common or distinct pathways?","volume":"62","author":"Pantopoulos","year":"2015","journal-title":"Hepatology"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"5705","DOI":"10.1021\/bi300752r","article-title":"Mechanisms of mammalian iron homeostasis","volume":"51","author":"Pantopoulos","year":"2012","journal-title":"Biochemistry"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"6421","DOI":"10.1074\/jbc.274.10.6421","article-title":"Translation of the alzheimer amyloid precursor protein mRNA is up-regulated by interleukin-1 through 5\u2032-untranslated region sequences","volume":"274","author":"Rogers","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Bandyopadhyay, S., Cahill, C., Balleidier, A., Huang, C., Lahiri, D.K., Huang, X., and Rogers, J.T. (2013). Novel 5\u2032 untranslated region directed blockers of iron-regulatory protein-1 dependent amyloid precursor protein translation: Implications for down syndrome and Alzheimer\u2019s disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065978"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s12031-002-0014-6","article-title":"Alzheimer\u2019s disease drug discovery targeted to the APP mRNA 5\u2032Untranslated region","volume":"19","author":"Rogers","year":"2002","journal-title":"J. Mol. Neurosci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"7605","DOI":"10.1073\/pnas.131152998","article-title":"Phenserine regulates translation of \u03b2-amyloid precursor protein mRNA by a putative interleukin-1 responsive element, a target for drug development","volume":"98","author":"Shaw","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1196\/annals.1332.003","article-title":"The integrated role of desferrioxamine and phenserine targeted to an iron-responsive element in the APP-mRNA 5\u2032-untranslated region","volume":"1035","author":"Venti","year":"2004","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1517\/14728222.2010.525352","article-title":"Novel drug targets based on metallobiology of Alzheimer\u2019s disease","volume":"14","author":"Bandyopadhyay","year":"2010","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2174\/156720506777632835","article-title":"RNA therapeutics directed to the non coding regions of APP mRNA, in vivo anti-amyloid efficacy of paroxetine, erythromycin, and N-acetyl cysteine","volume":"3","author":"Tucker","year":"2006","journal-title":"Curr. Alzheimer Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1002\/alz.12185","article-title":"Targeting increased levels of APP in Down syndrome: Posiphen-mediated reductions in APP and its products reverse endosomal phenotypes in the Ts65Dn mouse model","volume":"17","author":"Chen","year":"2020","journal-title":"Alzheimers Dement."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1124\/jpet.106.112102","article-title":"The Experimental Alzheimer\u2019s Disease Drug Posiphen [(+)-Phenserine] Lowers Amyloid-\u03b2 Peptide Levels in Cell Culture and Mice","volume":"320","author":"Lahiri","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jalz.2009.04.250","article-title":"Posiphen lowers amyloid precursor protein and amyloid \u03b2 as well as acetylcholinesterase levels in culture, animals and humans","volume":"5","author":"Maccecchini","year":"2009","journal-title":"Alzheimer\u2019s Dementia"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1111\/j.1471-4159.2006.04258.x","article-title":"Therapeutic targets and potential of the novel brain- permeable multifunctional iron chelator-monoamine oxidase inhibitor drug, M-30, for the treatment of Alzheimer\u2019s disease","volume":"100","author":"Amit","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1074\/jbc.C100614200","article-title":"An mRNA loop\/bulge in the ferritin iron-responsive element forms in vivo and was detected by radical probing with Cu-1,10-phenantholine and iron regulatory protein footprinting","volume":"277","author":"Ke","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1073\/pnas.0509744102","article-title":"The up-regulation of ferritin expression using a small-molecule ligand to the native mRNA","volume":"103","author":"Tibodeau","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1080\/17460441.2022.2084528","article-title":"A meditation on accelerating the development of small molecule medicines targeting RNA","volume":"18","author":"Yang","year":"2023","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/s41573-022-00521-4","article-title":"Targeting RNA structures with small molecules","volume":"21","author":"Yang","year":"2022","journal-title":"Nat. Rev. Drug Discov."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/12\/1669\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:51:53Z","timestamp":1760115113000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/12\/1669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,11]]},"references-count":152,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ph17121669"],"URL":"https:\/\/doi.org\/10.3390\/ph17121669","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,11]]}}}