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Methods: Gene set variation analysis (GSVA) scores were used to investigate the relationship between ferroptosis and AD. Logistic regression with seven feature selections and a deep learning model were utilized to identify potential targets of AMK based on transcriptomic data from multiple tissues. A transcriptome-wide association study (TWAS), summary-data-based mendelian randomization (SMR), and mendelian randomization (MR) were utilized to validate the causal relationship between target genes and AD risk. A single-gene gene set enrichment analysis (GSEA) was employed to investigate the biological pathways associated with the target genes. Three molecular docking strategies and a molecular dynamics simulation were employed to verify the binding domains interacting with AMK. Furthermore, the anti-AD effects of AMK were validated in a zebrafish AD model by testing behavior responses, apoptosis, and the deposition of beta-amyloid (A\u03b2) in the brain. Ultimately, real-time qPCR was used to verify the ferroptosis-related targets, which was identified via multi-omics. Results: Ferroptosis is an important pathogenic mechanism of AD, as suggested by the GSVA scores. AMK may exert its anti-AD activity through targets genes identified in the brain (ATP5MC3, GOT1, SAT1, EGFR, and MAPK9) and blood (G6PD, PGD, ALOX5, HMOX1, and ULK1). EGFR and HMOX1 were further confirmed as target genes mediating the anti-AD activity of AMK through TWAS, SMR, and MR analyses. The GSEA results indicated that EGFR may be involved in oxidative phosphorylation-related pathways, while HMOX1 may be associated with lysosome and phagosome pathways. The results of three molecular docking strategies and molecular dynamics simulations implied that the kinase domain of EGFR and the catalytic domain of HMOX1 played pivotal roles in the interaction between AMK and the targets. In a zebrafish model, AD-like symptoms including motor slowness and delayed responses, neuronal apoptosis, and plaque deposition in the brain, were significantly improved after AMK treatment. Accordingly, AMK reversed the abnormal expression of egfra and hmox1a, two core targets genes involved in ferroptosis. Conclusions: AMK significantly alleviated AD-like symptoms through the modulation of EGFR and HMOX1, which might reduce lipid peroxidation, thereby suppressing ferroptosis. This study provided evidence supporting the efficacy and therapeutic targets associated with ferroptosis in AMK-treated AD, which aid in the development of therapeutic interventions.<\/jats:p>","DOI":"10.3390\/cimb47020118","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T10:53:22Z","timestamp":1739271202000},"page":"118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploring the Efficacy and Target Genes of Atractylodes Macrocephala Koidz Against Alzheimer\u2019s Disease Based on Multi-Omics, Computational Chemistry, and Experimental Verification"],"prefix":"10.3390","volume":"47","author":[{"given":"Yuanteng","family":"Zheng","sequence":"first","affiliation":[{"name":"Biology Institute, Qilu University of Technology, Shandong Academy of Sciences, 28789 East Jingshi Road, Jinan 250103, China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Jinan 250103, China"},{"name":"School of Psychology, North China University of Science and Technology, 21 Bohai Road, Tangshan 063210, China"},{"name":"School of Public Health, North China University of Science and Technology, 21 Bohai Road, Tangshan 063210, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Gao","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology, Shandong Academy of Sciences, 28789 East Jingshi Road, Jinan 250103, China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Jinan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyang","family":"Tang","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology, Shandong Academy of Sciences, 28789 East Jingshi Road, Jinan 250103, China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Jinan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Gao","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology, Shandong Academy of Sciences, 28789 East Jingshi Road, Jinan 250103, China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Jinan 250103, China"},{"name":"School of Psychology, North China University of Science and Technology, 21 Bohai Road, Tangshan 063210, China"},{"name":"School of Public Health, North China University of Science and Technology, 21 Bohai Road, Tangshan 063210, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Cui","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology, Shandong Academy of Sciences, 28789 East Jingshi Road, Jinan 250103, China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Jinan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kechun","family":"Liu","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology, Shandong Academy of Sciences, 28789 East Jingshi Road, Jinan 250103, China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Jinan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiujun","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Psychology, North China University of Science and Technology, 21 Bohai Road, Tangshan 063210, China"},{"name":"School of Public Health, North China 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Implications for understanding the clinical phenotype of progressive neurodegenerative disease","volume":"19","author":"Jicha","year":"2010","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.3233\/JAD-2010-100975","article-title":"Alzheimer\u2019s disease: A general introduction and pathomechanism","volume":"22","author":"Finder","year":"2010","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Derry, P.J., Hegde, M.L., Jackson, G.R., Kayed, R., Tour, J.M., Tsai, A.-L., and Kent, T.A. (2020). Revisiting the intersection of amyloid, pathologically modified tau and iron in Alzheimer\u2019s disease from a ferroptosis perspective. Prog. Neurobiol., 184.","DOI":"10.1016\/j.pneurobio.2019.101716"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/2047-9158-2-6","article-title":"Traditional Chinese medicine: A promising candidate for the treatment of Alzheimer\u2019s disease","volume":"2","author":"Sun","year":"2013","journal-title":"Transl. Neurodegener."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5712187","DOI":"10.1155\/2020\/5712187","article-title":"Evaluation of the therapeutic effect of traditional Chinese medicine on osteoarthritis: A systematic review and meta-analysis","volume":"2020","author":"Wang","year":"2020","journal-title":"Pain Res. Manag."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100394","DOI":"10.1016\/j.prmcm.2024.100394","article-title":"A Comprehensive Pharmacological Review of Atractylodes Macrocephala: Traditional Uses, Phytochemistry, Pharmacokinetics, And Therapeutic Potential","volume":"10","author":"Singh","year":"2024","journal-title":"Pharmacol. Res. Mod. Chin. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.jep.2018.08.023","article-title":"The traditional uses, phytochemistry, and pharmacology of Atractylodes macrocephala Koidz.: A review","volume":"226","author":"Zhu","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"He, Y.-J., Cong, L., Liang, S.-L., Ma, X., Tian, J.-N., Li, H., and Wu, Y. (2022). Discovery and validation of Ferroptosis-related molecular patterns and immune characteristics in Alzheimer\u2019s disease. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.1056312"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"631","DOI":"10.2147\/CIA.S200109","article-title":"Effect of genetic polymorphisms on Alzheimer\u2019s disease treatment outcomes: An update","volume":"14","author":"Sumirtanurdin","year":"2019","journal-title":"Clin. Interv. Aging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8595","DOI":"10.18632\/aging.204359","article-title":"ESR1 dysfunction triggers neuroinflammation as a critical upstream causative factor of the Alzheimer\u2019s disease process","volume":"14","author":"Liu","year":"2022","journal-title":"Aging"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1038\/s41418-020-00685-9","article-title":"Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer\u2019s disease","volume":"28","author":"Bao","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Feng, H., and Stockwell, B.R. (2018). Unsolved mysteries: How does lipid peroxidation cause ferroptosis?. PLoS Biol., 16.","DOI":"10.1371\/journal.pbio.2006203"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"181","DOI":"10.2174\/1568026023394443","article-title":"Chemical and physical properties and potential mechanisms: Melatonin as a broad spectrum antioxidant and free radical scavenger","volume":"2","author":"Tan","year":"2002","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.fcij.2017.12.001","article-title":"Classification using deep learning neural networks for brain tumors","volume":"3","author":"Mohsen","year":"2018","journal-title":"Future Comput. Inform. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101354","DOI":"10.1016\/j.imu.2023.101354","article-title":"Novel machine learning based approach for analysing the adoption of metaverse in medical training: A UAE case study","volume":"42","author":"Salloum","year":"2023","journal-title":"Inform. Med. Unlocked"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2003893","DOI":"10.1002\/advs.202003893","article-title":"Machine learning identifies metabolic signatures that predict the risk of recurrent angina in remitted patients after percutaneous coronary intervention: A multicenter prospective cohort study","volume":"8","author":"Cui","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_17","first-page":"17","article-title":"Machine learning models and algorithms for big data classification","volume":"36","author":"Suthaharan","year":"2016","journal-title":"Integr. Ser. Inf. Syst."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1111\/1462-2920.15554","article-title":"Comparative genomics reveals a core gene toolbox for lifestyle transitions in Hypocreales fungi","volume":"23","author":"Wu","year":"2021","journal-title":"Environ. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1038\/s41588-019-0385-z","article-title":"Opportunities and challenges for transcriptome-wide association studies","volume":"51","author":"Wainberg","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Pantsar, T., and Poso, A. (2018). Binding affinity via docking: Fact and fiction. Molecules, 23.","DOI":"10.3390\/molecules23081899"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5110","DOI":"10.1021\/acs.jcim.1c00471","article-title":"Molecular mechanism of Ca2+ in the allosteric regulation of human parathyroid hormone receptor-1","volume":"62","author":"Li","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3714","DOI":"10.1038\/s41467-020-17437-5","article-title":"Protein\u2013ligand binding with the coarse-grained Martini model","volume":"11","author":"Souza","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/ije\/dyx207","article-title":"Mendelian randomization: A novel approach for the prediction of adverse drug events and drug repurposing opportunities","volume":"46","author":"Walker","year":"2017","journal-title":"Int. J. Epidemiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1002\/med.20067","article-title":"Combining docking and molecular dynamic simulations in drug design","volume":"26","author":"Alonso","year":"2006","journal-title":"Med. Res. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"D991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: Archive for functional genomics data sets\u2014Update","volume":"41","author":"Barrett","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"D896","DOI":"10.1093\/nar\/gkw1133","article-title":"The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog)","volume":"45","author":"MacArthur","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Elsworth, B., Lyon, M., Alexander, T., Liu, Y., Matthews, P., Hallett, J., Bates, P., Palmer, T., Haberland, V., and Smith, G.D. (2020). The MRC IEU OpenGWAS data infrastructure. BioRxiv.","DOI":"10.1101\/2020.08.10.244293"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e52155","DOI":"10.7554\/eLife.52155","article-title":"The single-cell eQTLGen consortium","volume":"9","author":"Groot","year":"2020","journal-title":"elife"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1038\/nn.4156","article-title":"The psychencode project","volume":"18","author":"Akbarian","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"D571","DOI":"10.1093\/nar\/gkac935","article-title":"FerrDb V2: Update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations","volume":"51","author":"Zhou","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"baq020","DOI":"10.1093\/database\/baq020","article-title":"GeneCards Version 3: The human gene integrator","volume":"2010","author":"Safran","year":"2010","journal-title":"Database"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Labonte, A.C., Kegerreis, B., Geraci, N.S., Bachali, P., Madamanchi, S., Robl, R., Catalina, M.D., Lipsky, P.E., and Grammer, A.C. (2018). Identification of alterations in macrophage activation associated with disease activity in systemic lupus erythematosus. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0208132"},{"key":"ref_33","first-page":"e62528","article-title":"Three differential expression analysis methods for RNA sequencing: Limma, EdgeR, DESeq2","volume":"175","author":"Liu","year":"2021","journal-title":"JoVE (J. Vis. Exp.)"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1093\/bioinformatics\/bts034","article-title":"The sva package for removing batch effects and other unwanted variation in high-throughput experiments","volume":"28","author":"Leek","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Langfelder, P., and Horvath, S. (2008). WGCNA: An R package for weighted correlation network analysis. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-559"},{"key":"ref_36","unstructured":"Hackeling, G. (2017). Mastering Machine Learning with Scikit-Learn, Packt Publishing Ltd."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Imambi, S., Prakash, K.B., and Kanagachidambaresan, G.P. (2021). Programming with TensorFlow: Solution for Edge Computing Applications, Springer.","DOI":"10.1007\/978-3-030-57077-4"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1002\/ijc.34761","article-title":"Regulome-wide association study identifies genetically driven accessible regions associated with pancreatic cancer risk","volume":"154","author":"Liu","year":"2024","journal-title":"Int. J. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1038\/s41467-018-03371-0","article-title":"Integrative analysis of omics summary data reveals putative mechanisms underlying complex traits","volume":"9","author":"Wu","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/s41588-023-01314-0","article-title":"Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk","volume":"55","author":"Shrine","year":"2023","journal-title":"Nat. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"D204","DOI":"10.1093\/nar\/gku989","article-title":"UniProt: A hub for protein information","volume":"43","author":"Consortium","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"D1102","DOI":"10.1093\/nar\/gky1033","article-title":"PubChem 2019 update: Improved access to chemical data","volume":"47","author":"Kim","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"W365","DOI":"10.1093\/nar\/gkx407","article-title":"HDOCK: A web server for protein\u2013protein and protein\u2013DNA\/RNA docking based on a hybrid strategy","volume":"45","author":"Yan","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"W363","DOI":"10.1093\/nar\/gki481","article-title":"PatchDock and SymmDock: Servers for rigid and symmetric docking","volume":"33","author":"Inbar","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"W229","DOI":"10.1093\/nar\/gkn186","article-title":"FireDock: A web server for fast interaction refinement in molecular docking","volume":"36","author":"Mashiach","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Daina, A., Michielin, O., and Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 7.","DOI":"10.1038\/srep42717"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1021\/ci990316u","article-title":"Combinatorial preferences affect molecular similarity\/diversity calculations using binary fingerprints and Tanimoto coefficients","volume":"40","author":"Godden","year":"2000","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"ref_49","unstructured":"Westerfield, M. (1995). The Zebrafish Book: A Guide for the Laboratory Use of Zebrafish (Brachydanio Rerio), University of Oregon Press."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"153662","DOI":"10.1016\/j.phymed.2021.153662","article-title":"Systems pharmacology approach uncovers the therapeutic mechanism of medicarpin against scopolamine-induced memory loss","volume":"91","author":"Li","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Belardo, C., Boccella, S., Perrone, M., Fusco, A., Morace, A.M., Ricciardi, F., Bonsale, R., ELBini-Dhouib, I., Guida, F., and Luongo, L. (2023). Scopolamine-Induced Memory Impairment in Mice: Effects of PEA-OXA on Memory Retrieval and Hippocampal LTP. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814399"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S1474-4422(08)70261-8","article-title":"Safety and efficacy of galantamine (Reminyl) in severe Alzheimer\u2019s disease (the SERAD study): A randomised, placebo-controlled, double-blind trial","volume":"8","author":"Burns","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.ecoenv.2019.01.104","article-title":"Synergistic effects of Pb and repeated heat pulse on developmental neurotoxicity in zebrafish","volume":"172","author":"Jin","year":"2019","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"106179","DOI":"10.1016\/j.envint.2020.106179","article-title":"Toxicity of different zinc oxide nanomaterials and dose-dependent onset and development of Parkinson\u2019s disease-like symptoms induced by zinc oxide nanorods","volume":"146","author":"Jin","year":"2021","journal-title":"Environ. Int."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/s41374-022-00779-7","article-title":"Inhibitory effects of temozolomide on glioma cells is sensitized by RSL3-induced ferroptosis but negatively correlated with expression of ferritin heavy chain 1 and ferritin light chain","volume":"102","author":"Yang","year":"2022","journal-title":"Lab. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/s41422-020-00441-1","article-title":"Ferroptosis: Molecular mechanisms and health implications","volume":"31","author":"Tang","year":"2021","journal-title":"Cell Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/s41586-021-03855-y","article-title":"Rare variant contribution to human disease in 281,104 UK Biobank exomes","volume":"597","author":"Wang","year":"2021","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.lfs.2006.12.014","article-title":"The relationship between erythropoietin pretreatment with blood\u2013brain barrier and lipid peroxidation after ischemia\/reperfusion in rats","volume":"80","author":"Bahcekapili","year":"2007","journal-title":"Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.3109\/10715762.2010.498478","article-title":"Pathological aspects of lipid peroxidation","volume":"44","author":"Auge","year":"2010","journal-title":"Free Radic. Res."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Chen, K., Jiang, X., Wu, M., Cao, X., Bao, W., and Zhu, L.-Q. (2021). Ferroptosis, a potential therapeutic target in Alzheimer\u2019s disease. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.704298"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Wang, Y.-Y., Sun, Y.-P., Luo, Y.-M., Peng, D.-H., Li, X., Yang, B.-Y., Wang, Q.-H., and Kuang, H.-X. (2021). Biomarkers for the clinical diagnosis of Alzheimer\u2019s disease: Metabolomics analysis of brain tissue and blood. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.700587"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.neuroscience.2015.03.006","article-title":"Hippocampal plasticity during the progression of Alzheimer\u2019s disease","volume":"309","author":"Mufson","year":"2015","journal-title":"Neuroscience"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"281","DOI":"10.2174\/1567205013666151218150322","article-title":"Defining the earliest pathological changes of Alzheimer\u2019s disease","volume":"13","author":"Vickers","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1159\/000356430","article-title":"The hippocampus in neurodegenerative disease","volume":"34","author":"Moodley","year":"2014","journal-title":"Hippocampus Clin. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Ain, Q.U., Sarfraz, M., Prasesti, G.K., Dewi, T.I., and Kurniati, N.F. (2021). Confounders in identification and analysis of inflammatory biomarkers in cardiovascular diseases. Biomolecules, 11.","DOI":"10.3390\/biom11101464"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Romano, R., and Bucci, C. (2020). Role of EGFR in the Nervous System. Cells, 9.","DOI":"10.3390\/cells9081887"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1016\/j.ajhg.2021.10.009","article-title":"Genome-wide analysis of common and rare variants via multiple knockoffs at biobank scale, with an application to Alzheimer disease genetics","volume":"108","author":"He","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Choi, H.-J., Jeong, Y.J., Kim, J., and Hoe, H.-S. (2023). EGFR is a potential dual molecular target for cancer and Alzheimer\u2019s disease. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1238639"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"146594","DOI":"10.1016\/j.gene.2022.146594","article-title":"Comprehensive analysis of placental gene-expression profiles and identification of EGFR-mediated autophagy and ferroptosis suppression in intrahepatic cholestasis of pregnancy","volume":"834","author":"Fang","year":"2022","journal-title":"Gene"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"101791","DOI":"10.1016\/j.arr.2022.101791","article-title":"Implicative role of epidermal growth factor receptor and its associated signaling partners in the pathogenesis of Alzheimer\u2019s disease","volume":"83","author":"Jayaswamy","year":"2023","journal-title":"Ageing Res. Rev."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Sung, H.Y., Choi, B.-O., Jeong, J.H., Kong, K.A., Hwang, J., and Ahn, J.-H. (2016). Amyloid beta-mediated hypomethylation of heme oxygenase 1 correlates with cognitive impairment in Alzheimer\u2019s disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153156"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Wang, J.-L., and Xu, C.-J. (2020). Astrocytes autophagy in aging and neurodegenerative disorders. Biomed. Pharmacother., 122.","DOI":"10.1016\/j.biopha.2019.109691"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1007\/s00125-017-4228-0","article-title":"HMOX1 as a marker of iron excess-induced adipose tissue dysfunction, affecting glucose uptake and respiratory capacity in human adipocytes","volume":"60","author":"Ortega","year":"2017","journal-title":"Diabetologia"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1080\/15548627.2018.1476812","article-title":"AT 101 induces early mitochondrial dysfunction and HMOX1 (heme oxygenase 1) to trigger mitophagic cell death in glioma cells","volume":"14","author":"Meyer","year":"2018","journal-title":"Autophagy"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1139\/o03-077","article-title":"SRC gene expression in human cancer: The role of transcriptional activation","volume":"82","author":"Dehm","year":"2004","journal-title":"Biochem. Cell Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1089\/ars.2010.3221","article-title":"Cancer chemoprevention mechanisms mediated through the Keap1\u2013Nrf2 pathway","volume":"13","author":"Hayes","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Peng, X., Sun, B., Tang, C., Shi, C., Xie, X., Wang, X., Jiang, D., Li, S., Jia, Y., and Wang, Y. (2024). HMOX1-LDHB interaction promotes ferroptosis by inducing mitochondrial dysfunction in foamy macrophages during advanced atherosclerosis. Dev. Cell.","DOI":"10.1016\/j.devcel.2024.12.011"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/2\/118\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:31:23Z","timestamp":1760027483000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/2\/118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,11]]},"references-count":77,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["cimb47020118"],"URL":"https:\/\/doi.org\/10.3390\/cimb47020118","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,11]]}}}