{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:42:50Z","timestamp":1791592970952,"version":"4.3.4"},"reference-count":76,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,2]],"date-time":"2025-02-02T00:00:00Z","timestamp":1738454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018990","name":"Alfaisal University","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":["Biomolecules"],"abstract":"<jats:p>\u03b1-Synuclein (\u03b1-Syn) is implicated in the pathophysiology of Parkinson\u2019s disease (PD) and plays a significant role in neuronal degeneration. Iron response proteins (IRPs) bind to iron response elements (IREs) found in the 5\u2032-untranslated regions (5\u2032-UTRs) of the messenger RNA that encode the \u03b1-Syn gene. This study used multi-spectroscopic approach techniques to investigate the impact of iron on \u03b1-Syn IRE RNA binding to IRP1. The formation of a stable complex between \u03b1-Syn RNA and IRP1 was suggested by fluorescence quenching results. Fluorescence measurements showed that \u03b1-Syn RNA and IRP1 had a strong interaction, with a binding constant (Ka) of 21.0 \u00d7 106 M\u22121 and 1:1 binding stoichiometry. About one binding site per IRP1 molecule was suggested by the \u03b1-Syn RNA binding. The Ka for \u03b1-Syn RNA\u2022IRP1 with added Fe2+ (50 \u03bcM) was 6.4 \u03bcM\u22121. When Fe2+ was added, the Ka of \u03b1-Syn RNA\u2022IRP1 was reduced by 3.3 times. These acquired Ka values were used to further understand the thermodynamic characteristics of \u03b1-Syn RNA\u2022IRP1 interactions. The thermodynamic properties clearly suggested that \u03b1-Syn RNA binding to IRP1 was an entropy-favored and enthalpy-driven event, with significant negative \u0394H and small positive \u0394S. For \u03b1-Syn RNA\u2022IRP1, the Gibbs free energy (\u0394G) was \u221243.7 \u00b1 2.7 kJ\/mol, but in the presence of Fe2+, it was \u221236.3 \u00b1 2.1 kJ\/mol. These thermodynamic calculations indicated that hydrogen bonding as well as van der Waals interactions might help to stabilize the complex formation. Additionally, far-UV CD spectra verified \u03b1-Syn RNA\u2022IRP1 complex formation, and \u03b1-Syn RNA and Fe2+ induce secondary structural alteration of IRP1. According to our findings, iron alters the hydrogen bonding in \u03b1-Syn RNA\u2022IRP1 complexes and induces a structural change in IRP1. This suggests that iron selectively affects the thermodynamics of these RNA\u2013protein interactions.<\/jats:p>","DOI":"10.3390\/biom15020214","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T05:36:32Z","timestamp":1738560992000},"page":"214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["\u03b1-Synuclein Iron-Responsive-Element RNA and Iron Regulatory Protein Affinity Is Specifically Reduced by Iron in Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2300-4595","authenticated-orcid":false,"given":"Mateen A.","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Life Sciences, College of Science & General Studies, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/s00702-017-1686-y","article-title":"Epidemiology of Parkinson\u2019s disease","volume":"124","author":"Tysnes","year":"2017","journal-title":"J. Neural Transm."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"\u03b1-synuclein in Lewy bodies","volume":"388","author":"Spillantini","year":"1997","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0140-6736(23)01478-2","article-title":"The pathogenesis of Parkinson\u2019s disease","volume":"403","author":"Morris","year":"2024","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1749-6632.2000.tb06900.x","article-title":"The \u03b1-synucleinopathies: Parkinson\u2019s disease, dementia with Lewy bodies, and multiple system atrophy","volume":"920","author":"Spillantini","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1126\/science.276.5321.2045","article-title":"Mutation in the \u03b1-synuclein gene identified in families with Parkinson\u2019s disease","volume":"276","author":"Polymeropoulos","year":"1997","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S51","DOI":"10.3233\/JPD-179005","article-title":"The Synucleinopathies: Twenty Years On","volume":"7","author":"Goedert","year":"2017","journal-title":"J. Parkinsons Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/ana.10795","article-title":"The new mutation, E46K, of \u03b1-synuclein causes Parkinson and Lewy body dementia","volume":"55","author":"Zarranz","year":"2004","journal-title":"Ann. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1002\/mds.25421","article-title":"\u03b1-synuclein p.H50Q, a novel pathogenic mutation for Parkinson\u2019s disease","volume":"28","author":"Encarnacion","year":"2013","journal-title":"Mov. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/S0140-6736(04)17104-3","article-title":"Causal relation between \u03b1-synuclein gene duplication and familial Parkinson\u2019s disease","volume":"364","author":"Kachergus","year":"2004","journal-title":"Lancet"},{"key":"ref_10","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_11","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/nchembio.1452","article-title":"Sequence-based design of bioactive small molecules that target precursor microRNAs","volume":"10","author":"Velagapudi","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1126\/science.1227157","article-title":"Pathological \u03b1-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice","volume":"338","author":"Luk","year":"2012","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s10286-021-00829-y","article-title":"Different phenoconversion pathways in pure autonomic failure with versus without Lewy bodies","volume":"31","author":"Goldstein","year":"2021","journal-title":"Clin. Auton. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Nechushtai, L., Frenkel, D., and Pinkas-Kramarski, R. (2023). Autophagy in Parkinson\u2019s Disease. Biomolecules, 13.","DOI":"10.3390\/biom13101435"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.tibs.2020.11.007","article-title":"Mitochondrial Dysfunction and Mitophagy in Parkinson\u2019s Disease: From Mechanism to Therapy","volume":"46","author":"Malpartida","year":"2021","journal-title":"Trends Biochem. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/ddr.21605","article-title":"Autophagy induction in the treatment of Alzheimer\u2019s disease","volume":"81","author":"Schmukler","year":"2020","journal-title":"Drug Dev. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"a024091","DOI":"10.1101\/cshperspect.a024091","article-title":"Cell Biology and Pathophysiology of \u03b1-Synuclein","volume":"8","author":"Sharma","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nature10324","article-title":"\u03b1-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation","volume":"477","author":"Bartels","year":"2011","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3827","DOI":"10.1038\/ncomms4827","article-title":"Direct observation of the three regions in \u03b1-synuclein that determine its membrane-bound behaviour","volume":"5","author":"Fusco","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.jmb.2009.03.021","article-title":"The first N-terminal amino acids of \u03b1-synuclein are essential for \u03b1-helical structure formation in vitro and membrane binding in yeast","volume":"389","author":"Vamvaca","year":"2009","journal-title":"J. Mol. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"22680","DOI":"10.1074\/jbc.M101181200","article-title":"Ca2+ binding to \u03b1-synuclein regulates ligand binding and oligomerization","volume":"276","author":"Nielsen","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/s41467-018-03111-4","article-title":"C-terminal calcium binding of \u03b1-synuclein modulates synaptic vesicle interaction","volume":"9","author":"Stephens","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Carapeto, A.P., Marcuello, C., Fa\u00edsca, P.F.N., and Rodrigues, M.S. (2024). Morphological and Biophysical Study of S100A9 Protein Fibrils by Atomic Force Microscopy Imaging and Nanomechanical Analysis. Biomolecules, 14.","DOI":"10.3390\/biom14091091"},{"key":"ref_24","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":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Khan, M.A. (2024). Targeting iron responsive elements (IREs) of APP mRNA into novel therapeutics to control the translation of amyloid-\u03b2 precursor protein in Alzheimer\u2019s disease. Pharmaceuticals, 17.","DOI":"10.3390\/ph17121669"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.mrfmmm.2003.08.004","article-title":"Labile iron pool: The main determinant of cellular response to oxidative stress","volume":"531","author":"Kruszewski","year":"2003","journal-title":"Mutat. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10737","DOI":"10.1074\/jbc.M010907200","article-title":"Evidence for a partially folded intermediate in \u03b1-synuclein fibril formation","volume":"276","author":"Uversky","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1093\/brain\/114.4.1953","article-title":"Alterations in the levels of iron, ferritin and other trace metals in Parkinson\u2019s disease and other neurodegenerative diseases affecting the basal ganglia","volume":"114","author":"Dexter","year":"1991","journal-title":"Brain"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1046\/j.1471-4159.2002.01118.x","article-title":"Lack of up-regulation of ferritin is associated with sustained iron regulatory protein-1 binding activity in the substantia nigra of patients with Parkinson\u2019s disease","volume":"83","author":"Faucheux","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1097\/WNR.0b013e328354a1f0","article-title":"\u03b1-Synuclein expression is modulated at the translational level by iron","volume":"23","author":"Febbraro","year":"2012","journal-title":"NeuroReport"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1039\/c6mt00026f","article-title":"\u03b1-synuclein: Relating metals to structure, function and inhibition","volume":"8","author":"McDowall","year":"2016","journal-title":"Met. Integr. Biometal Sci."},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/sj.mp.4001937","article-title":"The 5\u2032-untranslated region of Parkinson\u2019s disease \u03b1-synuclein messengerRNA contains a predicted iron responsive element","volume":"12","author":"Friedlich","year":"2007","journal-title":"Mol. Psychiatry"},{"key":"ref_34","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_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","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_38","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_39","doi-asserted-by":"crossref","unstructured":"Khan, M.A., Malik, A., Domashevskiy, A.V., San, A., and Khan, J.M. (2020). Interaction of ferritin iron responsive element (IRE) mRNA with translation initiation factor eIF4F. Spectrochim. Acta Part A Mol. Biomol. Spectrscopy, 243.","DOI":"10.1016\/j.saa.2020.118776"},{"key":"ref_40","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_41","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_42","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Reuter, J.S., and Mathews, D.H. (2010). RNAstructure: Software for RNA secondary structure prediction and analysis. BMC Bioinform., 11.","DOI":"10.1186\/1471-2105-11-129"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1093\/nar\/gkg595","article-title":"Mfold web server for nucleic acid folding and hybridization prediction","volume":"31","author":"Zuker","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Wang, J., and Xiao, Y. (2022). 3dRNA: 3D Structure Prediction from Linear to Circular RNAs. J. Mol. Biol., 434.","DOI":"10.1016\/j.jmb.2022.167452"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.ymeth.2016.03.010","article-title":"RNAComposer and RNA 3D structure prediction for nanotechnology","volume":"103","author":"Biesiada","year":"2016","journal-title":"Methods"},{"key":"ref_47","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_48","doi-asserted-by":"crossref","first-page":"4120","DOI":"10.1021\/bi00772a015","article-title":"Determination of the secondary structures of proteins by circular dichroism and optical rotatory dispersion","volume":"11","author":"Chen","year":"1972","journal-title":"Biochemistry"},{"key":"ref_49","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_50","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s10534-006-9063-6","article-title":"Coordinating responses to iron and oxygen stress with DNA and mRNA promoters: The ferritin story","volume":"20","author":"Theil","year":"2007","journal-title":"Biometals Int. J. Role Met. Ions Biol. Biochem. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.3390\/ijms10031226","article-title":"Physiological and pathological role of \u03b1-synuclein in Parkinson\u2019s disease through iron mediated oxidative stress; the role of a putative iron-responsive element","volume":"10","author":"Olivares","year":"2009","journal-title":"Int. J. Mol. Sci."},{"key":"ref_52","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_53","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_54","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_55","doi-asserted-by":"crossref","unstructured":"Shen, M., Goforth, J.B., and Eisenstein, R.S. (2023). Iron-dependent post transcriptional control of mitochondrial aconitase expression. Met. Integr. Biometal Sci., 15.","DOI":"10.1093\/mtomcs\/mfac099"},{"key":"ref_56","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_57","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_58","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_59","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_60","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s12551-020-00619-2","article-title":"Theory and applications of differential scanning fluorimetry in early-stage drug discovery","volume":"12","author":"Gao","year":"2020","journal-title":"Biophys. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.ab.2009.03.036","article-title":"Circular dichroism spectroscopy has intrinsic limitations for protein secondary structure analysis","volume":"389","author":"Khrapunov","year":"2009","journal-title":"Anal. Biochem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1385\/1-59259-912-5:343","article-title":"Circular dichroism spectroscopy for the study of protein-ligand interactions","volume":"305","author":"Rodger","year":"2005","journal-title":"Methods Mol. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1007\/s00253-013-5123-3","article-title":"Structural characteristics of thermostable immunogenic outer membrane protein from Salmonella enterica serovar Typhi","volume":"98","author":"Rabbani","year":"2014","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0141-8130(02)00017-X","article-title":"Bilirubin binding properties of pigeon serum albumin and its comparison with human serum albumin","volume":"30","author":"Khan","year":"2002","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_65","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_66","doi-asserted-by":"crossref","first-page":"15048","DOI":"10.1073\/pnas.0505148102","article-title":"DNA and mRNA elements with complementary responses to hemin, antioxidant inducers, and iron control ferritin-L expression","volume":"102","author":"Hintze","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","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_68","doi-asserted-by":"crossref","first-page":"3096","DOI":"10.1021\/bi00514a017","article-title":"Thermodynamics of protein association reactions: Forces contributing to stability","volume":"20","author":"Ross","year":"1981","journal-title":"Biochemistry"},{"key":"ref_69","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. (Elite Ed.), 14.","DOI":"10.31083\/j.fbe1403017"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.saa.2019.02.028","article-title":"Molecular interaction study of an anticancer drug, ponatinib with human serum albumin using spectroscopic and molecular docking methods","volume":"214","author":"Tayyab","year":"2019","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"9997","DOI":"10.1073\/pnas.96.18.9997","article-title":"The maximal affinity of ligands","volume":"96","author":"Kuntz","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1006\/jmbi.1996.0161","article-title":"RNA hairpins with non-nucleotide spacers bind efficiently to the human U1A protein","volume":"257","author":"Williams","year":"1996","journal-title":"J. Mol. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1515\/znc-1974-1-204","article-title":"Evidence for the validity of three-component fitting of protein circular dichroism spectra","volume":"29","author":"Bannister","year":"1974","journal-title":"Z. Naturforsch. C Biosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.bbrc.2010.08.017","article-title":"The universal mechanism for iron translocation to the ferroxidase site in ferritin, which is mediated by the well conserved transit site","volume":"400","author":"Masuda","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Khan, M.A., and Domashevskiy, A.V. (2021). Iron enhances the binding rates and translational efficiency of iron responsive elements (IREs) mRNA with initiation factor eIF4F. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0250374"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/S1474-4422(14)70117-6","article-title":"The role of iron in brain ageing and neurodegenerative disorders","volume":"13","author":"Ward","year":"2014","journal-title":"Lancet Neurol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/2\/214\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:25:47Z","timestamp":1760027147000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/2\/214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,2]]},"references-count":76,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["biom15020214"],"URL":"https:\/\/doi.org\/10.3390\/biom15020214","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,2]]}}}