{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:01:49Z","timestamp":1790863309088,"version":"4.1.0"},"reference-count":84,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Science Technology Council (NSTC) of Taiwan","award":["111-2320-B-182-012"],"award-info":[{"award-number":["111-2320-B-182-012"]}]},{"name":"the National Science Technology Council (NSTC) of Taiwan","award":["112-2320-B-182-027"],"award-info":[{"award-number":["112-2320-B-182-027"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a complex neurodegenerative disorder with multifaceted pathogenesis. Given the clinical need for multi-target interventions, this study elucidated the neuroprotective mechanisms of walnut (Juglans regia L.) against AD-related cognitive impairment. Methods: We characterized 25 bioactive constituents (fatty acids and ellagitannins) and constructed a protein\u2013protein interaction (PPI) network. GO\/KEGG enrichment, integrated with Ingenuity Pathway Analysis (IPA), deciphered pharmacological pathways, followed by molecular docking to evaluate ligand\u2013target binding thermodynamics. Network analysis revealed that walnut phytochemicals synergistically modulate the MAPK-mTORC1-TFEB-mediated endolysosomal homeostasis pathway. Molecular docking indicated that ellagitannins (strictinin, pedunculagin, tellimagrandin I) exhibit robust affinities for upstream RAS\/RAF\/MEK kinases, suppressing pro-pathogenic signaling. Concurrently, gallic acid targeted ABCA1 and TFEB, promoting TFEB activation and nuclear translocation to enhance beta-amyloid clearance and lysosomal biogenesis. This study provides evidence that walnut attenuates AD pathology through \u201cmulti-component\u201d reinforcement of the endolysosomal defense system, establishing a mechanistic foundation for walnut as a promising functional food.<\/jats:p>","DOI":"10.3390\/ijms27188288","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:18:26Z","timestamp":1790860706000},"page":"8288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Neuroprotective Effects of Walnut (Juglans regia L.) Against Cognitive Impairment in Alzheimer\u2019s Disease Through the MAPK-mTORC1-TFEB-Mediated Endolysosomal Pathway: A Network Pharmacology and Molecular Docking Approach"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5117-2791","authenticated-orcid":false,"given":"Chih-Ting","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Chinese Medicine, E-Da Cancer Hospital, Kaohsiung 82445, Taiwan"},{"name":"Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"},{"name":"School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 84001, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan-Tso","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chinese Medicine, E-Da Cancer Hospital, Kaohsiung 82445, Taiwan"},{"name":"School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 84001, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7490-4465","authenticated-orcid":false,"given":"Yu-Chiang","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Chinese Medicine, Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"},{"name":"Linsen Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei 10450, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41572-021-00269-y","article-title":"Alzheimer Disease","volume":"7","author":"Knopman","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s Disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100094","DOI":"10.1016\/j.tjpad.2025.100094","article-title":"Lecanemab for Early Alzheimer\u2019s Disease: Appropriate Use Recommendations from the French Federation of Memory Clinics","volume":"12","author":"Villain","year":"2025","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e12465","DOI":"10.1002\/trc2.12465","article-title":"Alzheimer\u2019s Disease Drug Development Pipeline: 2024","volume":"10","author":"Cummings","year":"2024","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/S1474-4422(25)00405-3","article-title":"Brain Amyloid on the Way to Dementia Prevention","volume":"24","author":"Frisoni","year":"2025","journal-title":"Lancet Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1056\/NEJMc2215148","article-title":"Multiple Cerebral Hemorrhages in a Patient Receiving Lecanemab and Treated with T-PA for Stroke","volume":"388","author":"Reish","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5989","DOI":"10.2174\/0109298673291838240311075415","article-title":"Predictive Analysis of Yi-Gai-San\u2019s Multifaceted Mechanisms for Tremor-Dominant Parkinson\u2019s Disease via Network Pharmacology and Molecular Docking Validation","volume":"31","author":"Lin","year":"2024","journal-title":"Curr. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.2174\/0109298673299665240924090617","article-title":"Multi-Target Mechanisms of Si-Ni-San on Anxious Insomnia: An Example of Network-Pharmacology and Molecular Docking Analysis","volume":"32","author":"Lin","year":"2025","journal-title":"Curr. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100543","DOI":"10.1016\/j.prmcm.2024.100543","article-title":"Traditional Chinese Medicine in Alzheimer\u2019s Disease: From the Perspective of GSK-3\u03b2 and Tau Hyperphosphorylation","volume":"13","author":"Wang","year":"2024","journal-title":"Pharmacol. Res. Mod.-Chin. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"105891","DOI":"10.1016\/j.jff.2023.105891","article-title":"Potential Anti-Alzheimer\u2019s Disease Effect of Defatted Walnut Powder through Remodeling Gut Microbiota and Modulating Amino Acid Metabolite Levels","volume":"111","author":"Xu","year":"2023","journal-title":"J. Funct. Foods"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3233\/ADR-230171","article-title":"Gallic Acid Alleviates Cognitive Impairment by Promoting Neurogenesis via the GSK3\u03b2-Nrf2 Signaling Pathway in an APP\/PS1 Mouse Model","volume":"8","author":"Ding","year":"2024","journal-title":"J. Alzheimer\u2019s Dis. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e13662","DOI":"10.1111\/acel.13662","article-title":"Urolithin A Improves Mitochondrial Health, Reduces Cartilage Degeneration, and Alleviates Pain in Osteoarthritis","volume":"21","author":"Olmer","year":"2022","journal-title":"Aging Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1093\/ajcn\/nqz328","article-title":"Effect of a 2-Year Diet Intervention with Walnuts on Cognitive Decline. The Walnuts And Healthy Aging (WAHA) Study: A Randomized Controlled Trial","volume":"111","author":"Rajaram","year":"2020","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Chauhan, A., and Chauhan, V. (2020). Beneficial Effects of Walnuts on Cognition and Brain Health. Nutrients, 12.","DOI":"10.3390\/nu12020550"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1007\/s12603-014-0569-2","article-title":"A Cross Sectional Study of the Association between Walnut Consumption and Cognitive Function among Adult US Populations Represented in NHANES","volume":"19","author":"Arab","year":"2015","journal-title":"J. Nutr. Health Aging"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nrd.2017.22","article-title":"Pharmacological Modulation of Autophagy: Therapeutic Potential and Persisting Obstacles","volume":"16","author":"Galluzzi","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e12833","DOI":"10.1002\/jimd.12833","article-title":"Unifying Biology of Neurodegeneration in Lysosomal Storage Diseases","volume":"48","author":"Ludlaim","year":"2025","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13024-025-00825-0","article-title":"Decoding Microglial Immunometabolism: A New Frontier in Alzheimer\u2019s Disease Research","volume":"20","author":"Jung","year":"2025","journal-title":"Mol. Neurodegener."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.1021\/acs.jafc.0c07798","article-title":"Characterization and Exploration of Potential Neuroprotective Peptides in Walnut (Juglans Regia) Protein Hydrolysate against Cholinergic System Damage and Oxidative Stress in Scopolamine-Induced Cognitive and Memory Impairment Mice and Zebrafish","volume":"69","author":"Wang","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1515\/jcim-2025-0278","article-title":"In Silico Evaluation of Bioactive Compounds as Potential Inhibitors Targeting HIF-1\u03b1\/VEGFA\/BACE1 Pathway against Alzheimer\u2019s Disease","volume":"23","author":"Rai","year":"2026","journal-title":"J. Complement. Integr. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Banc, R., Rusu, M.E., Filip, L., and Popa, D.-S. (2023). The Impact of Ellagitannins and Their Metabolites through Gut Microbiome on the Gut Health and Brain Wellness within the Gut\u2013Brain Axis. Foods, 12.","DOI":"10.3390\/foods12020270"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Rudrapal, M., Rakshit, G., Singh, R.P., Garse, S., Khan, J., and Chakraborty, S. (2024). Dietary Polyphenols: Review on Chemistry\/Sources, Bioavailability\/Metabolism, Antioxidant Effects, and Their Role in Disease Management. Antioxidants, 13.","DOI":"10.3390\/antiox13040429"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s12974-019-1450-3","article-title":"Urolithin A Attenuates Memory Impairment and Neuroinflammation in APP\/PS1 Mice","volume":"16","author":"Gong","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.4103\/1673-5374.335163","article-title":"Urolithin A Alleviates Blood-Brain Barrier Disruption and Attenuates Neuronal Apoptosis Following Traumatic Brain Injury in Mice","volume":"17","author":"Gong","year":"2022","journal-title":"Neural Regen. Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Dai, K., Agarwal, N., Rodriguez-Palacios, A., and Basson, A.R. (2024). Regulation of Intestinal Inflammation by Walnut-Derived Bioactive Compounds. Nutrients, 16.","DOI":"10.3390\/nu16162643"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kawabata, K., Yoshioka, Y., and Terao, J. (2019). Role of Intestinal Microbiota in the Bioavailability and Physiological Functions of Dietary Polyphenols. Molecules, 24.","DOI":"10.3390\/molecules24020370"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.devcel.2020.06.010","article-title":"The Lysosome at the Intersection of Cellular Growth and Destruction","volume":"54","author":"Shin","year":"2020","journal-title":"Dev. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s12964-023-01097-1","article-title":"mTOR-Dependent TFEB Activation and TFEB Overexpression Enhance Autophagy-Lysosome Pathway and Ameliorate Alzheimer\u2019s Disease-like Pathology in Diabetic Encephalopathy","volume":"21","author":"Cheng","year":"2023","journal-title":"Cell Commun. Signal"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Di Matteo, F., Vietri, M., D\u2019Alessio, S., Ciaglia, T., Vestuto, E.F., Pepe, G., Moltedo, O., Di Sarno, V., Musella, S., and Ostacolo, C. (2025). Targeting Cathepsins in Neurodegeneration: Biochemical Advances. Biomedicines, 13.","DOI":"10.3390\/biomedicines13123019"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.7150\/ijbs.103028","article-title":"Regulatory Mechanisms and Therapeutic Implications of Lysosomal Dysfunction in Alzheimer\u2019s Disease","volume":"21","author":"Kim","year":"2025","journal-title":"Int. J. Biol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"116511","DOI":"10.1016\/j.ejmech.2024.116511","article-title":"Structure-Based Design of Multitargeting ChEs-MAO B Inhibitors Based on Phenyl Ring Bioisosteres: AChE\/BChE Selectivity Switch and Drug-like Characterization","volume":"274","author":"Miniero","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Almaghrabi, M. (2025). Multitarget-Directed Ligands for Alzheimer\u2019s Disease: Recent Novel MTDLs and Mechanistic Insights. Pharmaceuticals, 18.","DOI":"10.3390\/ph18111685"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.freeradbiomed.2021.07.013","article-title":"Defective Mitophagy and Synaptic Degeneration in Alzheimer\u2019s Disease: Focus on Aging, Mitochondria and Synapse","volume":"172","author":"Morton","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/s41419-020-2322-6","article-title":"Pharmacological Enhancement of TFEB-Mediated Autophagy Alleviated Neuronal Death in Oxidative Stress-Induced Parkinson\u2019s Disease Models","volume":"11","author":"Zhuang","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"105855","DOI":"10.1016\/j.nbd.2022.105855","article-title":"TFEB in Alzheimer\u2019s Disease: From Molecular Mechanisms to Therapeutic Implications","volume":"173","author":"Gu","year":"2022","journal-title":"Neurobiol. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e1388252025","DOI":"10.1523\/JNEUROSCI.1388-25.2025","article-title":"APOE-Targeted Therapeutics for Alzheimer\u2019s Disease","volume":"45","author":"Yassine","year":"2025","journal-title":"J. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/s41420-024-01850-6","article-title":"From the Regulatory Mechanism of TFEB to Its Therapeutic Implications","volume":"10","author":"Chen","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"102649","DOI":"10.1016\/j.jbc.2022.102649","article-title":"TFEB Acetylation Promotes Lysosome Biogenesis and Ameliorates Alzheimer\u2019s Disease\u2013Relevant Phenotypes in Mice","volume":"298","author":"Li","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1159\/000067426","article-title":"The Role of Mitogen-Activated Protein Kinase Pathways in Alzheimer\u2019s Disease","volume":"11","author":"Zhu","year":"2002","journal-title":"Neurosignals"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"116631","DOI":"10.1016\/j.ejmech.2024.116631","article-title":"An Overview of RAF Kinases and Their Inhibitors (2019\u20132023)","volume":"275","author":"Hashem","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41586-019-1694-1","article-title":"The Clinical KRAS(G12C) Inhibitor AMG 510 Drives Anti-Tumour Immunity","volume":"575","author":"Canon","year":"2019","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Esselun, C., Dieter, F., Sus, N., Frank, J., and Eckert, G.P. (2022). Walnut Oil Reduces A\u03b2 Levels and Increases Neurite Length in a Cellular Model of Early Alzheimer Disease. Nutrients, 14.","DOI":"10.3390\/nu14091694"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"23083","DOI":"10.1021\/acsomega.2c00336","article-title":"Insights into the Interaction between Polyphenols and \u03b2-Lactoglobulin through Molecular Docking, MD Simulation, and QM\/MM Approaches","volume":"7","author":"Baruah","year":"2022","journal-title":"ACS Omega"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hadidi, M., Li\u00f1\u00e1n-Atero, R., Tarahi, M., Christodoulou, M.C., and Aghababaei, F. (2024). The Potential Health Benefits of Gallic Acid: Therapeutic and Food Applications. Antioxidants, 13.","DOI":"10.3390\/antiox13081001"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1007\/s12017-020-08639-7","article-title":"A Walnut Diet in Combination with Enriched Environment Improves Cognitive Function and Affects Lipid Metabolites in Brain and Liver of Aged NMRI Mice","volume":"23","author":"Esselun","year":"2021","journal-title":"Neuromolecular Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Tow, W.-K., Chee, P.-Y., Sundralingam, U., and Palanisamy, U.D. (2022). The Therapeutic Relevance of Urolithins, Intestinal Metabolites of Ellagitannin-Rich Food: A Systematic Review of In Vivo Studies. Nutrients, 14.","DOI":"10.3390\/nu14173494"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"112927","DOI":"10.1016\/j.exger.2025.112927","article-title":"\u03b1-Lipoic Acid Mitigates Age-Related Cognitive Decline by Modulating PPAR\u03b3\/NF-\u03baB-Mediated Neuroinflammation","volume":"215","author":"Zhang","year":"2026","journal-title":"Exp. Gerontol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"123042","DOI":"10.1016\/j.biomaterials.2024.123042","article-title":"Ultrasmall Iron-Gallic Acid Coordination Polymer Nanoparticles for Scavenging ROS and Suppressing Inflammation in Tauopathy-Induced Alzheimer\u2019s Disease","volume":"317","author":"Huang","year":"2025","journal-title":"Biomaterials"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.neuron.2008.04.010","article-title":"ApoE Promotes the Proteolytic Degradation of Abeta","volume":"58","author":"Jiang","year":"2008","journal-title":"Neuron"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e2213670120","DOI":"10.1073\/pnas.2213670120","article-title":"A Small-Molecule Drug Inhibits Autophagy Gene Expression through the Central Regulator TFEB","volume":"120","author":"Lin","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1080\/15548627.2016.1179404","article-title":"A Novel Curcumin Analog Binds to and Activates TFEB in Vitro and in Vivo Independent of MTOR Inhibition","volume":"12","author":"Song","year":"2016","journal-title":"Autophagy"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s13020-020-00402-1","article-title":"Transcription Factor EB Agonists from Natural Products for Treating Human Diseases with Impaired Autophagy-Lysosome Pathway","volume":"15","author":"Xu","year":"2020","journal-title":"Chin. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"927","DOI":"10.2174\/1389450118666170328122527","article-title":"Natural Polyphenols in the Treatment of Alzheimer\u2019s Disease","volume":"19","author":"Zulfarina","year":"2018","journal-title":"Curr. Drug Targets"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3591","DOI":"10.2174\/1381612826666201112144006","article-title":"Neuroprotective Effects of Ellagic Acid in Alzheimer\u2019s Disease: Focus on Underlying Molecular Mechanisms of Therapeutic Potential","volume":"27","author":"Javaid","year":"2021","journal-title":"Curr. Pharm. Des."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"115352","DOI":"10.1016\/j.ejmech.2023.115352","article-title":"Bioisosteric Replacement Based on 1,2,4-Oxadiazoles in the Discovery of 1H-Indazole-Bearing Neuroprotective MAO B Inhibitors","volume":"255","author":"Rullo","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"117107","DOI":"10.1016\/j.jep.2023.117107","article-title":"Neuroprotective Mechanisms of Defatted Walnut Powder against Scopolamine-Induced Alzheimer\u2019s Disease in Mice Revealed through Metabolomics and Proteomics Analyses","volume":"319","author":"Xu","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Moon, J.H., Kim, J.M., Lee, U., Kang, J.Y., Kim, M.J., Lee, H.L., Jeong, H.R., Go, M.J., Kim, H.-J., and Park, H.W. (2022). Walnut Prevents Cognitive Impairment by Regulating the Synaptic and Mitochondrial Dysfunction via JNK Signaling and Apoptosis Pathway in High-Fat Diet-Induced C57BL\/6 Mice. Molecules, 27.","DOI":"10.3390\/molecules27165316"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.molmed.2021.04.009","article-title":"Impact of the Natural Compound Urolithin A on Health, Disease, and Aging","volume":"27","author":"Andreux","year":"2021","journal-title":"Trends Mol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/alzrt182","article-title":"Comprehensive Behavioral Characterization of an APP\/PS-1 Double Knock-in Mouse Model of Alzheimer\u2019s Disease","volume":"5","author":"Webster","year":"2013","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"102327","DOI":"10.1016\/j.fbio.2022.102327","article-title":"Effects of Walnut (Juglans Regia L.) Kernel Extract and Juglone on Dopamine Levels and Oxidative Stress in Rats","volume":"51","author":"Cintesun","year":"2023","journal-title":"Food Biosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"106292","DOI":"10.1016\/j.jff.2024.106292","article-title":"Astounding the Synergistic Interplay of Walnuts in Combating Inflammation and Oxidative Damage","volume":"119","author":"Shabbir","year":"2024","journal-title":"J. Funct. Foods"},{"key":"ref_62","first-page":"e42550","article-title":"Urolithin A as a Potential Agent for Prevention of Age-Related Disease: A Scoping Review","volume":"15","author":"Kothe","year":"2023","journal-title":"Cureus"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Zhang, R., Zhu, X., Bai, H., and Ning, K. (2019). Network Pharmacology Databases for Traditional Chinese Medicine: Review and Assessment. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00123"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Ye, X., Wang, H., Cheng, S., Xia, L., Xu, X., and Li, X. (2022). Network Pharmacology-Based Strategy to Investigate the Pharmacologic Mechanisms of Coptidis Rhizoma for the Treatment of Alzheimer\u2019s Disease. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.890046"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING Database in 2023: Protein-Protein Association Networks and Functional Enrichment Analyses for Any Sequenced Genome of Interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"6646","DOI":"10.1038\/s41467-024-50983-w","article-title":"SR-TWAS: Leveraging Multiple Reference Panels to Improve Transcriptome-Wide Association Study Power by Ensemble Machine Learning","volume":"15","author":"Parrish","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Cao, W., Ji, Z., Zhu, S., Wang, M., and Sun, R. (2024). Bioinformatic Identification and Experiment Validation Reveal 6 Hub Genes, Promising Diagnostic and Therapeutic Targets for Alzheimer\u2019s Disease. BMC Med. Genom., 17.","DOI":"10.1186\/s12920-023-01775-6"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e71139","DOI":"10.1002\/fsn3.71139","article-title":"Combining Network Pharmacology, Molecular Docking, and Integrative Studies to Explore the Mechanism of Helminthostachys Zeylanica in Alleviating Ulcerative Colitis","volume":"13","author":"Lin","year":"2025","journal-title":"Food Sci. Nutr."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Tan, B., Wang, Y., Zhang, X., and Sun, X. (2022). Recent Studies on Protective Effects of Walnuts against Neuroinflammation. Nutrients, 14.","DOI":"10.3390\/nu14204360"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/s41586-022-05652-7","article-title":"Structure of the Lysosomal mTORC1\u2013TFEB\u2013Rag\u2013Ragulator Megacomplex","volume":"614","author":"Cui","year":"2023","journal-title":"Nature"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","article-title":"Causal Analysis Approaches in Ingenuity Pathway Analysis","volume":"30","author":"Green","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_72","first-page":"831","article-title":"A Simple Click by Click Protocol to Perform Docking: AutoDock 4.2 Made Easy for Non-Bioinformaticians","volume":"12","author":"Rizvi","year":"2013","journal-title":"EXCLI J."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Mirza, F.J., Zahid, S., Amber, S., Jabeen, H., Asim, N., and Ali Shah, S.A. (2022). Multitargeted Molecular Docking and Dynamic Simulation Studies of Bioactive Compounds from Rosmarinus Officinalis against Alzheimer\u2019s Disease. Molecules, 27.","DOI":"10.3390\/molecules27217241"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e70496","DOI":"10.1002\/fsn3.70496","article-title":"Polyphenols and Alzheimer\u2019s Disease: A Review on Molecular and Therapeutic Insights With In Silico Support","volume":"13","author":"Chen","year":"2025","journal-title":"Food Sci. Nutr."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1023\/A:1008175606698","article-title":"Chemical composition of walnuts (Juglans regia L.) grown in New Zealand","volume":"56","author":"Savage","year":"2001","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4884","DOI":"10.1111\/1750-3841.17186","article-title":"Comparison of chemical compositions and aroma characteristics of walnut oil prepared by different roasting processes","volume":"89","author":"Lu","year":"2024","journal-title":"J. Food Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.jfca.2013.06.004","article-title":"Comparative study of the nutritional and bioactive compounds content of four walnut (Juglans regia L.) cultivars","volume":"31","author":"Tapia","year":"2013","journal-title":"J. Food Compos. Anal."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"328","DOI":"10.3989\/gya.2005.v56.i4.101","article-title":"Fatty acid composition of some walnuts (Juglans regia L.) cultivars from east Anatolia","volume":"156","author":"Dogan","year":"2005","journal-title":"Grasas Aceites"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.3390\/ijms13021561","article-title":"Composition, structure and functional properties of protein concentrates and isolates produced from walnut (Juglans regia L.)","volume":"13","author":"Mao","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_80","first-page":"270","article-title":"Identification and quantification of phenolic compounds in walnuts","volume":"173","author":"Slatnar","year":"2015","journal-title":"Food Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.foodchem.2013.11.158","article-title":"Comprehensive identification of walnut polyphenols by liquid chromatography coupled to linear ion trap-Orbitrap mass spectrometry","volume":"152","author":"Regueiro","year":"2014","journal-title":"Food Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jfca.2018.09.016","article-title":"Identification and quantification of phytosterols in black walnut kernels","volume":"75","author":"Vu","year":"2019","journal-title":"J. Food Compos. Anal."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Mu\u00f1oz-Esparza, N.C., Costa-Catala, J., Comas-Bast\u00e9, O., Toro-Funes, N., Latorre-Moratalla, M.L., Veciana-Nogu\u00e9s, M.T., and Vidal-Carou, M.C. (2021). Occurrence of Polyamines in Foods and the Influence of Cooking Processes. Foods, 10.","DOI":"10.3390\/foods10081752"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.foodres.2018.03.066","article-title":"Characterization of virgin walnut oils and their residual cakes produced from different varieties","volume":"108","author":"Salvador","year":"2018","journal-title":"Food Res. Int."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8288\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:19:18Z","timestamp":1790860758000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":84,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27188288"],"URL":"https:\/\/doi.org\/10.3390\/ijms27188288","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]}}}