{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:07:25Z","timestamp":1791284845840,"version":"4.1.0"},"reference-count":86,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T00:00:00Z","timestamp":1674864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Galantamine is a natural alkaloid extracted from the Amaryllidaceae plants and is used as the active ingredient of a drug approved for the treatment of the early stages of Alzheimer\u2019s disease. It mainly acts as an acetylcholinesterase (AChE) inhibitor, increasing concentrations of the acetylcholine neurotransmitter. Recent cellular studies have also shown the ability of galantamine to protect SH-SY5Y cell lines against amyloid-\u03b2 (A\u03b2)-induced toxicity. Such investigations have supported and validated further in-depth studies for understanding the chemical and molecular features associated with galantamine-protective abilities. In addition to galantamine, other natural alkaloids are known to possess AChE inhibitory activity; among them lycorine has been extensively investigated for its antibacterial, anti-inflammatory and antitumoral activities as well. Despite its interesting biological properties, lycorine\u2019s neuroprotective functions against A\u03b2-induced damages have not been explored so far. In this research study, the ability of galantamine and lycorine to suppress A\u03b2-induced in vitro neuronal toxicity was evaluated by investigating the chemical interactions of the two alkaloids with A\u03b2 peptide. A multi-technique spectroscopic analysis and cellular cytotoxicity assays were applied to obtain new insights on these molecular associations. The comparison between the behaviors exhibited by the two alkaloids indicates that both compounds possess analogue abilities to interact with the amyloidogenic peptide and protect cells.<\/jats:p>","DOI":"10.3390\/ijms24032500","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T04:58:25Z","timestamp":1675054705000},"page":"2500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["A Comparative Study between Lycorine and Galantamine Abilities to Interact with AMYLOID \u03b2 and Reduce In Vitro Neurotoxicity"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9803-9015","authenticated-orcid":false,"given":"Arian","family":"Kola","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2788-8797","authenticated-orcid":false,"given":"Stefania","family":"Lamponi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Curr\u00f2","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4187-3919","authenticated-orcid":false,"given":"Daniela","family":"Valensin","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy"},{"name":"CIRMMP, Via Luigi Sacconi 6, 50019 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s Disease","volume":"397","author":"Kivipelto","year":"2021","journal-title":"Lancet"},{"key":"ref_2","unstructured":"Patterson, C. (2018). World Alzheimer Report 2018: The State of the Art of Dementia Research\u2014New Frontiers, Alzheimer\u2019s Disease International."},{"key":"ref_3","unstructured":"Gauthier, S., Rosa-Neto, P., Morais, J.A., and Webster, C. (2021). World Alzheimer Report 2021: Journey through the Diagnosis of Dementia, Alzheimer\u2019s Disease International."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"114578","DOI":"10.1016\/j.ejmech.2022.114578","article-title":"Molecular Mechanisms in Alzheimer\u2019s Disease and Related Potential Treatments Such as Structural Target Convergence of Antibodies and Simple Organic Molecules","volume":"240","author":"Oumata","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"106735","DOI":"10.1016\/j.bpc.2021.106735","article-title":"A Mechanistic Survey of Alzheimer\u2019s Disease","volume":"281","author":"Tang","year":"2022","journal-title":"Biophys. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.biopsych.2020.02.001","article-title":"The \u03b2-Secretase BACE1 in Alzheimer\u2019s Disease","volume":"89","author":"Hampel","year":"2021","journal-title":"Biol. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101391","DOI":"10.1016\/j.arr.2021.101391","article-title":"Living with the Enemy: From Protein-Misfolding Pathologies We Know, to Those We Want to Know","volume":"70","author":"Emwas","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101619","DOI":"10.1016\/j.arr.2022.101619","article-title":"Oxidative Stress: The Core Pathogenesis and Mechanism of Alzheimer\u2019s Disease","volume":"77","author":"Bai","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.redox.2017.10.014","article-title":"Oxidative Stress and the Amyloid Beta Peptide in Alzheimer\u2019s Disease","volume":"14","author":"Cheignon","year":"2018","journal-title":"Redox Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13561","DOI":"10.1021\/acs.inorgchem.9b01399","article-title":"CuII Binding Properties of N-Truncated A\u03b2 Peptides: In Search of Biological Function","volume":"58","author":"Stefaniak","year":"2019","journal-title":"Inorg. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1007\/s10072-020-04321-9","article-title":"Using NMR Spectroscopy to Investigate the Role Played by Copper in Prion Diseases","volume":"41","author":"Alsiary","year":"2020","journal-title":"Neurol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1021\/cr040410w","article-title":"Copper Homeostasis and Neurodegenerative Disorders (Alzheimer\u2019s, Prion and Parkinson\u2019s Diseases and Amyotrophic Lateral Sclerosis)","volume":"106","author":"Gaggelli","year":"2006","journal-title":"Chem. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1016\/j.ccr.2012.04.006","article-title":"Metal Ions in Neurodegenerative Diseases","volume":"256","author":"Faller","year":"2012","journal-title":"Coord. Chem. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1016\/j.ccr.2012.05.003","article-title":"Metal Ions and Amyloid Fiber Formation in Neurodegenerative Diseases. Copper, Zinc and Iron in Alzheimer\u2019s, Parkinson\u2019s and Prion Diseases","volume":"256","author":"Viles","year":"2012","journal-title":"Coord. Chem. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1016\/j.ccr.2012.04.010","article-title":"Metal Compounds as Inhibitors of \u03b2-Amyloid Aggregation. Perspectives for an Innovative Metallotherapeutics on Alzheimer\u2019s Disease","volume":"256","author":"Valensin","year":"2012","journal-title":"Coord. Chem. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1016\/j.ccr.2012.03.013","article-title":"Copper, Zinc and Iron in Neurodegenerative Diseases (Alzheimer\u2019s, Parkinson\u2019s and Prion Diseases)","volume":"256","author":"Kozlowski","year":"2012","journal-title":"Coord. Chem. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Pardo-Moreno, T., Gonz\u00e1lez-Acedo, A., Rivas-Dom\u00ednguez, A., Garc\u00eda-Morales, V., Garc\u00eda-Cozar, F.J., Ramos-Rodr\u00edguez, J.J., and Melguizo-Rodr\u00edguez, L. (2022). Therapeutic Approach to Alzheimer\u2019s Disease: Current Treatments and New Perspectives. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14061117"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wang, S., Kong, X., Chen, Z., Wang, G., Zhang, J., and Wang, J. (2022). Role of Natural Compounds and Target Enzymes in the Treatment of Alzheimer\u2019s Disease. Molecules, 27.","DOI":"10.3390\/molecules27134175"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13195-020-00663-w","article-title":"Aducanumab, Gantenerumab, BAN2401 and ALZ-801-the First Wave of Amyloid-Targeting Drugs for Alzheimer\u2019s Disease with Potential for near Term Approval","volume":"12","author":"Tolar","year":"2020","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"(2021). Filling the Void for New Alzheimer\u2019s Disease Therapy. Nat. Aging, 1, 567\u2013568.","DOI":"10.1038\/s43587-021-00092-w"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"eabb5924","DOI":"10.1126\/sciadv.abb5924","article-title":"Small-Molecule Sequestration of Amyloid-\u03b2 as a Drug Discovery Strategy for Alzheimer\u2019s Disease","volume":"6","author":"Heller","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e61453","DOI":"10.7554\/eLife.61453","article-title":"The Metal Cofactor Zinc and Interacting Membranes Modulate SOD1 Conformation-Aggregation Landscape in an in Vitro ALS Model","volume":"10","author":"Sannigrahi","year":"2021","journal-title":"eLife"},{"key":"ref_23","unstructured":"(1993). Tacrine Granted Marketing Approval for Alzheimer\u2019s Disease. Clin. Pharm., 12, 873\u2013876."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.1093\/ajhp\/54.24.2805","article-title":"Donepezil: An Anticholinesterase Inhibitor for Alzheimer\u2019s Disease","volume":"54","author":"Shintani","year":"1997","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1093\/ajhp\/57.21.1942","article-title":"FDA Approves New Cholinesterase Inhibitor for Alzheimer\u2019s Disease","volume":"57","author":"Miller","year":"2000","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1093\/ajhp\/58.8.649a","article-title":"FDA Approves Galantamine for Alzheimer\u2019s Disease","volume":"58","author":"Thompson","year":"2001","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Tuzimski, T., and Petruczynik, A. (2022). Determination of Anti-Alzheimer\u2019s Disease Activity of Selected Plant Ingredients. Molecules, 27.","DOI":"10.3390\/molecules27103222"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Dhahri, M., Alghrably, M., Mohammed, H.A., Badshah, S.L., Noreen, N., Mouffouk, F., Rayyan, S., Qureshi, K.A., Mahmood, D., and Lachowicz, J.I. (2021). Natural Polysaccharides as Preventive and Therapeutic Horizon for Neurodegenerative Diseases. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14010001"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7278","DOI":"10.2174\/0929867328666210729120242","article-title":"Metal Complexation Mechanisms of Polyphenols Associated to Alzheimer\u2019s Disease","volume":"28","author":"Kola","year":"2021","journal-title":"Curr. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kola, A., Hecel, A., Lamponi, S., and Valensin, D. (2020). Novel Perspective on Alzheimer\u2019s Disease Treatment: Rosmarinic Acid Molecular Interplay with Copper(II) and Amyloid \u03b2. Life, 10.","DOI":"10.3390\/life10070118"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Cahl\u00edkov\u00e1, L., Vrabec, R., Pidan\u00fd, F., Pe\u0159inov\u00e1, R., Maafi, N., Mamun, A.A., Ritomsk\u00e1, A., Wijaya, V., and Blunden, G. (2021). Recent Progress on Biological Activity of Amaryllidaceae and Further Isoquinoline Alkaloids in Connection with Alzheimer\u2019s Disease. Molecules, 26.","DOI":"10.3390\/molecules26175240"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.lfs.2014.12.011","article-title":"Neuroprotective Activity and Acetylcholinesterase Inhibition of Five Amaryllidaceae Species: A Comparative Study","volume":"122","author":"Cortes","year":"2015","journal-title":"Life Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1080\/10286020.2016.1198332","article-title":"Phytochemical and Biological Investigations of Amaryllidaceae Alkaloids: A Review","volume":"19","author":"Ding","year":"2017","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"16562","DOI":"10.1039\/C4RA14666B","article-title":"Biological and Pharmacological Activities of Amaryllidaceae Alkaloids","volume":"5","author":"He","year":"2015","journal-title":"RSC Adv."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Koirala, M., Karimzadegan, V., Liyanage, N.S., M\u00e9rindol, N., and Desgagn\u00e9-Penix, I. (2022). Biotechnological Approaches to Optimize the Production of Amaryllidaceae Alkaloids. Biomolecules, 12.","DOI":"10.3390\/biom12070893"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Masi, M., Di Lecce, R., Cimmino, A., and Evidente, A. (2020). Advances in the Chemical and Biological Characterization of Amaryllidaceae Alkaloids and Natural Analogues Isolated in the Last Decade. Molecules, 25.","DOI":"10.3390\/molecules25235621"},{"key":"ref_37","unstructured":"Kalola, U.K., and Nguyen, H. (2022). Galantamine, StatPearls Publishing."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.neuro.2007.11.004","article-title":"Antioxidative Properties of Galantamine on Neuronal Damage Induced by Hydrogen Peroxide in SK-N-SH Cells","volume":"29","author":"Ezoulin","year":"2008","journal-title":"Neurotoxicology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/j.1600-079X.2010.00778.x","article-title":"Synergistic Neuroprotective Effect of Combined Low Concentrations of Galantamine and Melatonin against Oxidative Stress in SH-SY5Y Neuroblastoma Cells","volume":"49","author":"Romero","year":"2010","journal-title":"J. Pineal Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1124\/jpet.105.090365","article-title":"Unequal Neuroprotection Afforded by the Acetylcholinesterase Inhibitors Galantamine, Donepezil, and Rivastigmine in SH-SY5Y Neuroblastoma Cells: Role of Nicotinic Receptors","volume":"315","author":"Arias","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.exger.2010.06.008","article-title":"Effects of Galantamine on \u03b2-Amyloid Release and Beta-Site Cleaving Enzyme 1 Expression in Differentiated Human Neuroblastoma SH-SY5Y Cells","volume":"45","author":"Li","year":"2010","journal-title":"Exp. Gerontol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jns.2009.01.024","article-title":"Galantamine Inhibits Beta-Amyloid Aggregation and Cytotoxicity","volume":"280","author":"Matharu","year":"2009","journal-title":"J. Neurol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.neuro.2016.10.013","article-title":"Galanthamine Decreases Genotoxicity and Cell Death Induced by \u03b2-Amyloid Peptide in SH-SY5Y Cell Line","volume":"57","author":"Castillo","year":"2016","journal-title":"Neurotoxicology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.neulet.2010.06.005","article-title":"Galantamine Inhibits Calpain-Calcineurin Signaling Activated by Beta-Amyloid in Human Neuroblastoma SH-SY5Y Cells","volume":"480","author":"Li","year":"2010","journal-title":"Neurosci. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1007\/s11101-021-09790-0","article-title":"The Amaryllidaceae Alkaloids: An Untapped Source of Acetylcholinesterase Inhibitors","volume":"21","author":"Berkov","year":"2021","journal-title":"Phytochem. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.jpba.2014.09.022","article-title":"Alkaloid Metabolite Profiles by GC\/MS and Acetylcholinesterase Inhibitory Activities with Binding-Mode Predictions of Five Amaryllidaceae Plants","volume":"102","author":"Cortes","year":"2015","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1055\/s-2004-818919","article-title":"Acetylcholinesterase Enzyme Inhibitory Effects of Amaryllidaceae Alkaloids","volume":"70","author":"Elgorashi","year":"2004","journal-title":"Planta Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"154266","DOI":"10.1016\/j.phymed.2022.154266","article-title":"Lycorine and Organ Protection: Review of Its Potential Effects and Molecular Mechanisms","volume":"104","author":"Xiao","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.micpath.2017.12.037","article-title":"Antibacterial Activity and Virtual Screening by Molecular Docking of Lycorine from Pancratium foetidum Pom (Moroccan Endemic Amaryllidaceae)","volume":"115","author":"Bendaif","year":"2018","journal-title":"Microb Pathog"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1159\/000487457","article-title":"Lycorine Suppresses Endplate-Chondrocyte Degeneration and Prevents Intervertebral Disc Degeneration by Inhibiting NF-\u039aB Signalling Pathway","volume":"45","author":"Wang","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.intimp.2011.11.018","article-title":"Lycorine Inhibits Lipopolysaccharide-Induced INOS and COX-2 up-Regulation in RAW264.7 Cells through Suppressing P38 and STATs Activation and Increases the Survival Rate of Mice after LPS Challenge","volume":"12","author":"Kang","year":"2012","journal-title":"Int. Immunopharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s11427-016-0368-y","article-title":"Lycorine Inhibits Breast Cancer Growth and Metastasis via Inducing Apoptosis and Blocking Src\/FAK-Involved Pathway","volume":"60","author":"Ying","year":"2017","journal-title":"Sci. China Life Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/1475-2867-12-49","article-title":"Lycorine Induces Cell-Cycle Arrest in the G0\/G1 Phase in K562 Cells via HDAC Inhibition","volume":"12","author":"Li","year":"2012","journal-title":"Cancer Cell Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6244","DOI":"10.1021\/jm901031h","article-title":"Lycorine, the Main Phenanthridine Amaryllidaceae Alkaloid, Exhibits Significant Antitumor Activity in Cancer Cells That Display Resistance to Proapoptotic Stimuli: An Investigation of Structure-Activity Relationship and Mechanistic Insight","volume":"52","author":"Andolfi","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5290","DOI":"10.1016\/j.bmcl.2010.06.130","article-title":"Structure-Activity Studies on Acetylcholinesterase Inhibition in the Lycorine Series of Amaryllidaceae Alkaloids","volume":"20","author":"McNulty","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4814","DOI":"10.1080\/14786419.2020.1727471","article-title":"Isoquinoline Alkaloids Reduce Beta-Amyloid Peptide Toxicity in Caenorhabditis Elegans","volume":"35","author":"Chacon","year":"2021","journal-title":"Nat. Prod. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e13307","DOI":"10.1111\/acel.13307","article-title":"Lycorine Hydrochloride Suppresses Stress-Induced Premature Cellular Senescence by Stabilizing the Genome of Human Cells","volume":"20","author":"Zhang","year":"2021","journal-title":"Aging Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.mrgentox.2018.06.010","article-title":"Caliphruria subedentata (Amaryllidaceae) Decreases Genotoxicity and Cell Death Induced by \u03b2-Amyloid Peptide in SH-SY5Y Cell Line","volume":"836","author":"Castillo","year":"2018","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"619667","DOI":"10.3389\/fnins.2020.619667","article-title":"Natural Compounds as Inhibitors of A\u03b2 Peptide Aggregation: Chemical Requirements and Molecular Mechanisms","volume":"14","author":"Pagano","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5672","DOI":"10.1016\/j.csbj.2022.10.014","article-title":"Big Dynorphin Is a Neuroprotector Scaffold against Amyloid \u03b2-Peptide Aggregation and Cell Toxicity","volume":"20","author":"Wallin","year":"2022","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"102852","DOI":"10.1016\/j.isci.2021.102852","article-title":"The Amyloid-Inhibiting NCAM-PrP Peptide Targets A\u03b2 Peptide Aggregation in Membrane-Mimetic Environments","volume":"24","author":"Vosough","year":"2021","journal-title":"iScience"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1021\/ac020563o","article-title":"Transferred Nuclear Overhauser Effect in Nuclear Magnetic Resonance Diffusion Measurements of Ligand-Protein Binding","volume":"75","author":"Lucas","year":"2003","journal-title":"Anal. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1146\/annurev.biophys.34.040204.144419","article-title":"Ligand-Target Interactions: What Can We Learn from NMR?","volume":"34","author":"Carlomagno","year":"2005","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4565","DOI":"10.2741\/3549","article-title":"Ligand Based NMR Methods for Drug Discovery","volume":"14","author":"Ludwig","year":"2009","journal-title":"Front. Biosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.arcmed.2012.12.004","article-title":"Ethanol Reduces Amyloid Aggregation in Vitro and Prevents Toxicity in Cell Lines","volume":"44","author":"Romero","year":"2013","journal-title":"Arch. Med. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.ijbiomac.2021.08.198","article-title":"Caffeic Acid for the Prevention and Treatment of Alzheimer\u2019s Disease: The Effect of Lipid Membranes on the Inhibition of Aggregation and Disruption of A\u03b2 Fibrils","volume":"190","author":"Andrade","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"101662","DOI":"10.1016\/j.jbc.2022.101662","article-title":"The Calcium-Free Form of Atorvastatin Inhibits Amyloid-\u03b2(1\u201342) Aggregation In Vitro","volume":"298","author":"Nedaei","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.ijbiomac.2017.03.001","article-title":"Vitamin B12 Offers Neuronal Cell Protection by Inhibiting A\u03b2-42 Amyloid Fibrillation","volume":"99","author":"Alam","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"12737","DOI":"10.1021\/bi701079z","article-title":"Three Histidine Residues of Amyloid-\u03b2 Peptide Control the Redox Activity of Copper and Iron","volume":"46","author":"Nakamura","year":"2007","journal-title":"Biochemistry"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1002\/cbic.200700111","article-title":"Redox Chemistry of Copper\u2013Amyloid-\u03b2: The Generation of Hydroxyl Radical in the Presence of Ascorbate Is Linked to Redox-Potentials and Aggregation State","volume":"8","author":"Guilloreau","year":"2007","journal-title":"ChemBioChem"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5909","DOI":"10.1021\/acs.analchem.8b00740","article-title":"Ascorbate Oxidation by Cu(Amyloid-\u03b2) Complexes: Determination of the Intrinsic Rate as a Function of Alterations in the Peptide Sequence Revealing Key Residues for Reactive Oxygen Species Production","volume":"90","author":"Faller","year":"2018","journal-title":"Anal. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1002\/ptr.6560","article-title":"Genistein Protects against Amyloid-Beta-Induced Toxicity in SH-SY5Y Cells by Regulation of Akt and Tau Phosphorylation","volume":"34","author":"Petry","year":"2020","journal-title":"Phytother. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1021\/acs.biochem.5b01259","article-title":"Monomeric A\u03b21-40 and A\u03b21-42 Peptides in Solution Adopt Very Similar Ramachandran Map Distributions That Closely Resemble Random Coil","volume":"55","author":"Roche","year":"2016","journal-title":"Biochemistry"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.jpba.2007.07.029","article-title":"The Thermodynamic Dissociation Constants of Four Non-Steroidal Anti-Inflammatory Drugs by the Least-Squares Nonlinear Regression of Multiwavelength Spectrophotometric PH-Titration Data","volume":"45","author":"Meloun","year":"2007","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_75","unstructured":"(2022, September 20). T3DB: Lycorine. Available online: http:\/\/www.t3db.ca\/toxins\/T3D4064."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1002\/pro.2319","article-title":"In Silico and In Vitro Studies to Elucidate the Role of Cu2+ and Galanthamine as the Limiting Step in the Amyloid Beta (1\u201342) Fibrillation Process","volume":"22","year":"2013","journal-title":"Protein Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.bmcl.2012.10.111","article-title":"Investigating the Binding Interactions of Galantamine with \u03b2-Amyloid Peptide","volume":"23","author":"Rao","year":"2013","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/978-1-62703-640-5_2","article-title":"Considerations for the Use of SH-SY5Y Neuroblastoma Cells in Neurobiology","volume":"1078","author":"Kovalevich","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/0045-6039(84)90038-1","article-title":"Retinoic Acid-Induced Differentiation of Cultured Human Neuroblastoma Cells: A Comparison with Phorbolester-Induced Differentiation","volume":"14","author":"Ruusala","year":"1984","journal-title":"Cell Differ."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0165-3806(87)90156-8","article-title":"Muscarinic Receptors in Human SH-SY5Y Neuroblastoma Cell Line: Regulation by Phorbol Ester and Retinoic Acid-Induced Differentiation","volume":"430","author":"Adem","year":"1987","journal-title":"Brain Res."},{"key":"ref_81","first-page":"53193","article-title":"Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line","volume":"108","author":"Shipley","year":"2016","journal-title":"J. Vis. Exp."},{"key":"ref_82","unstructured":"(2022, November 30). Guarire con le Piante Medicinali\u2014Volume 1. Available online: https:\/\/www.aseq.it\/medicina-e-discipline-corporee\/43936-guarire-con-le-piante-medicinali-volume-1.html."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"166","DOI":"10.3109\/13506120009146831","article-title":"An Improved Method of Preparing the Amyloid \u03b2-Protein for Fibrillogenesis and Neurotoxicity Experiments","volume":"7","author":"Fezoui","year":"2000","journal-title":"Amyloid"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1006\/jmre.1998.1598","article-title":"Multiple-Pulse Mixing Sequences That Selectively Enhance Chemical Exchange or Cross-Relaxation Peaks in High-Resolution NMR Spectra","volume":"135","author":"Hwang","year":"1998","journal-title":"J. Magn. Reson."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Savitzky, A., and Golay, M.J.E (1964). Smoothing and Differentiation of Data by Simplified Least Squares Procedures. Anal. Chem., 36, 1627\u20131639.","DOI":"10.1021\/ac60214a047"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"7717","DOI":"10.1073\/pnas.1203193109","article-title":"Toxic Fibrillar Oligomers of Amyloid-\u03b2 Have Cross-\u03b2 Structure","volume":"109","author":"Stroud","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2500\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:17:34Z","timestamp":1760120254000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,28]]},"references-count":86,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24032500"],"URL":"https:\/\/doi.org\/10.3390\/ijms24032500","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,28]]}}}