{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T14:50:27Z","timestamp":1778251827286,"version":"3.51.4"},"reference-count":89,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education","award":["2020R1I1A1A01060627"],"award-info":[{"award-number":["2020R1I1A1A01060627"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type 2 Diabetes (T2D) is characterized by the toxic aggregation of human islet amyloid polypeptide (hIAPP or amylin) within pancreatic \u03b2-cells. IAPP is also a neuropancreatic hormone that plays a significant role in Alzheimer\u2019s disease (AD) by co-depositing with amyloid-beta (A\u03b2) and Tau, supporting the Type 3 Diabetes (T3D) hypothesis. Soluble IAPP accelerates A\u03b2 aggregation through cross-seeding and causes neurotoxicity by impairing the blood\u2013brain barrier and activating neuroinflammation. Melatonin inhibits these processes by disrupting hydrophobic interactions in both hIAPP and A\u03b2, preventing the formation of toxic \u03b2-sheet structures. Furthermore, melatonin promotes amyloid clearance via the glymphatic and lymphatic systems, protects neurons from oxidative damage, and reduces Tau hyperphosphorylation. This suggests that melatonin serves as a promising multitarget therapeutic agent for both metabolic and neurodegenerative disorders by modulating structural protein transformations.<\/jats:p>","DOI":"10.3390\/ijms27062910","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T15:54:53Z","timestamp":1774281293000},"page":"2910","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Physiological Implications of Pancreatic Amyloid Polypeptide Aggregation and Its Inhibition by Melatonin"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1732-8494","authenticated-orcid":false,"given":"Yeong-Min","family":"Yoo","sequence":"first","affiliation":[{"name":"Institute of Environmental Research, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3449-0645","authenticated-orcid":false,"given":"Seong Soo","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Marine Bioscience, College of Life Science, Kangwon National University, Gangneung 25457, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1038\/nm1066","article-title":"Protein aggregation and neurodegenerative disease","volume":"10","author":"Ross","year":"2004","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1146\/annurev-pathol-020712-163913","article-title":"AA amyloidosis: Pathogenesis and targeted therapy","volume":"10","author":"Westermark","year":"2015","journal-title":"Annu. Rev. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1016\/j.jmb.2008.11.006","article-title":"Molecular mechanism of thioflavin-T binding to the surface of beta-rich peptide self-assemblies","volume":"385","author":"Biancalana","year":"2009","journal-title":"J. Mol. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1021\/jp309528f","article-title":"Thioflavine-T and Congo Red reveal the polymorphism of insulin amyloid fibrils when probed by polarization-resolved fluorescence microscopy","volume":"117","author":"Duboisset","year":"2013","journal-title":"J. Phys. Chem. B"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3629","DOI":"10.1210\/jc.2004-0405","article-title":"Islet amyloid: A critical entity in the pathogenesis of type 2 diabetes","volume":"89","author":"Hull","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ghosh, P., Kumar, A., Datta, B., and Rangachari, V. (2010). Dynamics of protofibril elongation and association involved in A\u03b242 peptide aggregation in Alzheimer\u2019s disease. BMC Bioinform., 11.","DOI":"10.1186\/1471-2105-11-S6-S24"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Foster, J.S., Balachandran, M., Hancock, T.J., Martin, E.B., Macy, S., Wooliver, C., Richey, T., Stuckey, A., Williams, A.D., and Jackson, J.W. (2023). Development and characterization of a prototypic pan-amyloid clearing agent\u2014A novel murine peptide-immunoglobulin fusion. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1275372"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Andrikopoulos, N., Tang, H., Wang, Y., Liang, X., Li, Y., Davis, T.P., and Ke, P.C. (2024). Exploring Peptido-Nanocomposites in the Context of Amyloid Diseases. Angew. Chem. Int. Ed. Engl., 63.","DOI":"10.1002\/anie.202309958"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2940","DOI":"10.1111\/j.1742-4658.2010.07721.x","article-title":"Mysterious oligomerization of the amyloidogenic proteins","volume":"277","author":"Uversky","year":"2010","journal-title":"FEBS J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1139\/cjpp-2015-0117","article-title":"Inhibition of islet amyloid polypeptide aggregation and associated cytotoxicity by nonsteroidal anti-inflammatory drugs","volume":"94","author":"Fortin","year":"2016","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Raimundo, A.F., Ferreira, S., Martins, I.C., and Menezes, R. (2020). Islet Amyloid Polypeptide: A Partner in Crime with A\u03b2 in the Pathology of Alzheimer\u2019s Disease. Front. Mol. Neurosci., 13.","DOI":"10.3389\/fnmol.2020.00035"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1152\/physrev.00042.2009","article-title":"Islet amyloid polypeptide, islet amyloid, and diabetes mellitus","volume":"91","author":"Westermark","year":"2011","journal-title":"Physiol. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/ana.23956","article-title":"Amylin deposition in the brain: A second amyloid in Alzheimer disease?","volume":"74","author":"Jackson","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1002\/ana.24992","article-title":"Brain microvascular injury and white matter disease provoked by diabetes-associated hyperamylinemia","volume":"82","author":"Ly","year":"2017","journal-title":"Ann. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"305101","DOI":"10.1088\/1361-6528\/ad403b","article-title":"Localized surface plasmon resonance and atomic force microscopy study of model lipid membranes and their interactions with amyloid and melatonin","volume":"35","author":"Mei","year":"2024","journal-title":"Nanotechnology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.18632\/aging.202457","article-title":"Efficacy of melatonin in animal models of intracerebral hemorrhage: A systematic review and meta-analysis","volume":"13","author":"Zeng","year":"2021","journal-title":"Aging"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/jcb.240550004","article-title":"Molecular physiology of amylin","volume":"55","author":"Pittner","year":"1994","journal-title":"J. Cell. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1007\/BF00405079","article-title":"Amylin-induced in vivo insulin resistance in conscious rats: The liver is more sensitive to amylin than peripheral tissues","volume":"34","author":"Koopmans","year":"1991","journal-title":"Diabetologia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5035","DOI":"10.1210\/endo.142.11.8593","article-title":"Inhibition of central amylin signaling increases food intake and body adiposity in rats","volume":"142","author":"Rushing","year":"2001","journal-title":"Endocrinology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/978-981-15-3262-7_11","article-title":"Natural Polyphenols as Modulators of the Fibrillization of Islet Amyloid Polypeptide","volume":"1250","author":"Reis","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1016\/S0140-6736(25)01776-3","article-title":"Amylin and the renin-angiotensin system: Risk or opportunity in amylin-based therapy?","volume":"406","author":"Muskiet","year":"2026","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"El Assar, M., Angulo, J., Santos-Ruiz, M., Moreno, P., Novials, A., Villanueva-Pe\u00f1acarrillo, M.L., and Rodr\u00edguez-Ma\u00f1as, L. (2015). Differential effect of amylin on endothelial-dependent vasodilation in mesenteric arteries from control and insulin resistant rats. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120479"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Bortoletto, A.S., Graham, W.V., Trout, G., Bonito-Oliva, A., Kazmi, M.A., Gong, J., Weyburne, E., Houser, B.L., Sakmar, T.P., and Parchem, R.J. (2022). Human Islet Amyloid Polypeptide (hIAPP) Protofibril-Specific Antibodies for Detection and Treatment of Type 2 Diabetes. Adv. Sci., 9.","DOI":"10.1002\/advs.202202342"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Pang, B., Zhuang, X., Bian, X., Liu, S., Liu, Z., and Song, F. (2020). Studies on the cross-interaction between hIAPP and A\u03b225-35 and the aggregation process in binary mixture by electrospray ionization-ion mobility-mass spectrometry. J. Mass Spectrom., 55.","DOI":"10.1002\/jms.4643"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"19556","DOI":"10.1038\/s41598-024-70255-3","article-title":"IAPP\u2014Oligomerisation levels in plasma of people with type 2 diabetes","volume":"14","author":"Rehn","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1152\/physiolgenomics.00029.2024","article-title":"Dysregulation of cholesterol homeostasis is an early signal of \u03b2-cell proteotoxicity characteristic of type 2 diabetes","volume":"56","author":"Gurlo","year":"2024","journal-title":"Physiol. Genom."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1084\/jem.20161134","article-title":"Induction of IAPP amyloid deposition and associated diabetic abnormalities by a prion-like mechanism","volume":"214","author":"Mukherjee","year":"2017","journal-title":"J. Exp. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2046327","DOI":"10.1155\/2016\/2046327","article-title":"Inhibition of IAPP Aggregation and Toxicity by Natural Products and Derivatives","volume":"2016","author":"Pithadia","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1515\/hsz-2020-0176","article-title":"Myricetin protects pancreatic \u03b2-cells from human islet amyloid polypeptide (hIAPP) induced cytotoxicity and restores islet function","volume":"402","author":"Dubey","year":"2020","journal-title":"Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"10913","DOI":"10.1021\/acs.jpcb.0c07830","article-title":"Theoretical Investigation of the Inhibitory Mechanism of Norepinephrine on hIAPP Amyloid Aggregation and the Destabilization of Protofibrils","volume":"124","author":"Roy","year":"2020","journal-title":"J. Phys. Chem. B"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Moya-Gudi\u00f1o, V., Altamirano-Bustamante, N.F., Revilla-Monsalve, C., and Altamirano-Bustamante, M.M. (2025). Decoding the Contribution of IAPP Amyloid Aggregation to Beta Cell Dysfunction: A Systematic Review and Epistemic Meta-Analysis of Type 1 Diabetes. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26020767"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1021\/ar200189b","article-title":"Membrane disruption and early events in the aggregation of the diabetes related peptide IAPP from a molecular perspective","volume":"45","author":"Brender","year":"2012","journal-title":"Acc. Chem. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1002\/jcp.30600","article-title":"Islet amyloid toxicity: From genesis to counteracting mechanisms","volume":"237","author":"Marmentini","year":"2022","journal-title":"J. Cell. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1074\/jbc.271.4.1988","article-title":"Pore formation by the cytotoxic islet amyloid peptide amylin","volume":"271","author":"Mirzabekov","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2798269","DOI":"10.1155\/2016\/2798269","article-title":"Islet Amyloid Polypeptide: Structure, Function, and Pathophysiology","volume":"2016","author":"Akter","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.4161\/auto.28478","article-title":"UCHL1 deficiency exacerbates human islet amyloid polypeptide toxicity in \u03b2-cells: Evidence of interplay between the ubiquitin\/proteasome system and autophagy","volume":"10","author":"Costes","year":"2014","journal-title":"Autophagy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3634","DOI":"10.1172\/JCI69866","article-title":"Human IAPP-induced pancreatic \u03b2 cell toxicity and its regulation by autophagy","volume":"124","author":"Shigihara","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s11010-016-2864-1","article-title":"Receptor-mediated toxicity of human amylin fragment aggregated by short- and long-term incubations with copper ions","volume":"425","author":"Caruso","year":"2017","journal-title":"Mol. Cell. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1093\/ilar.47.3.225","article-title":"Islet amyloid polypeptide (IAPP) transgenic rodents as models for type 2 diabetes","volume":"47","author":"Matveyenko","year":"2006","journal-title":"ILAR J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S41","DOI":"10.1007\/BF00586278","article-title":"Cellular and molecular biology of the beta cell","volume":"35","author":"Steiner","year":"1992","journal-title":"Diabetologia"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/dom.13401","article-title":"Islet prohormone processing in health and disease","volume":"20","author":"Chen","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1152\/physrev.00008.2021","article-title":"Altered islet prohormone processing: A cause or consequence of diabetes?","volume":"102","author":"Ramzy","year":"2022","journal-title":"Physiol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9228","DOI":"10.1021\/bi0510936","article-title":"Characterization of the heparin binding site in the N-terminus of human pro-islet amyloid polypeptide: Implications for amyloid formation","volume":"45","author":"Abedini","year":"2006","journal-title":"Biochemistry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"105083","DOI":"10.1016\/j.chemphyslip.2021.105083","article-title":"Investigation of the effects of two major secretory granules components, insulin and zinc, on human-IAPP amyloid aggregation and membrane damage","volume":"237","author":"Khemtemourian","year":"2021","journal-title":"Chem. Phys. Lipids"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.jmb.2010.12.028","article-title":"Inhibition of glycosaminoglycan-mediated amyloid formation by islet amyloid polypeptide and proIAPP processing intermediates","volume":"406","author":"Meng","year":"2011","journal-title":"J. Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0925-4439(01)00078-3","article-title":"Islet amyloid and type 2 diabetes: From molecular misfolding to islet pathophysiology","volume":"1537","author":"Jaikaran","year":"2001","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.neuroscience.2024.04.002","article-title":"The Co-oligomers of A\u03b242 and Human Islet Amyloid Polypeptide Exacerbate Neurotoxicity and Alzheimer-like Pathology at Cellular Level","volume":"547","author":"Deng","year":"2024","journal-title":"Neuroscience"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1038\/mp.2016.230","article-title":"Molecular interaction between type 2 diabetes and Alzheimer\u2019s disease through cross-seeding of protein misfolding","volume":"22","author":"Edwards","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13195-023-01375-7","article-title":"The fluorescent ligand bTVBT2 reveals increased p-tau uptake by retinal microglia in Alzheimer\u2019s disease patients and AppNL-F\/NL-F mice","volume":"16","author":"Andersson","year":"2024","journal-title":"Alzheimers Res. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Stanciu, G.D., Bild, V., Ababei, D.C., Rusu, R.N., Cobzaru, A., Paduraru, L., and Bulea, D. (2020). Link Between Diabetes and Alzheimer\u2019s Disease due to the Shared Amyloid Aggregation and Deposition Involving both Neurodegenerative Changes and Neurovascular Damages. J. Clin. Med., 9.","DOI":"10.3390\/jcm9061713"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Michailidis, M., Moraitou, D., Tata, D.A., Kalinderi, K., Papamitsou, T., and Papaliagkas, V. (2022). Alzheimer\u2019s Disease as Type 3 Diabetes: Common Pathophysiological Mechanisms between Alzheimer\u2019s Disease and Type 2 Diabetes. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052687"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s11418-020-01467-w","article-title":"Effects of clovamide and its related compounds on the aggregations of amyloid polypeptides","volume":"75","author":"Nomoto","year":"2021","journal-title":"J. Nat. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.4103\/1673-5374.300323","article-title":"Islet amyloid polypeptide & amyloid beta peptide roles in Alzheimer\u2019s disease: Two triggers, one disease","volume":"16","author":"Ferreira","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Siddiqui, F., Mishra, P., Khanam, S., Ranjan, S., Alam, P., Albalawi, T., Khan, S., and Mir, S.S. (2025). Nano-Chaperones: Bridging Therapeutics for Amyloid Aggregation in Alzheimer\u2019s Disease and Type-2 Diabetes Mellitus. Eur. J. Neurosci., 61.","DOI":"10.1111\/ejn.70142"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1021\/acschemneuro.7b00396","article-title":"Islet Amyloid Polypeptide Promotes Amyloid-Beta Aggregation by Binding-Induced Helix-Unfolding of the Amyloidogenic Core","volume":"9","author":"Ge","year":"2018","journal-title":"ACS Chem. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3703","DOI":"10.1021\/acschemneuro.9b00260","article-title":"Blocking Inflammasome Activation Caused by \u03b2-Amyloid Peptide (A\u03b2) and Islet Amyloid Polypeptide (IAPP) through an IAPP Mimic","volume":"10","author":"Aftabizadeh","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1007\/s00125-008-1111-z","article-title":"Calcium elevation in mouse pancreatic beta cells evoked by extracellular human islet amyloid polypeptide involves activation of the mechanosensitive ion channel TRPV4","volume":"51","author":"Casas","year":"2008","journal-title":"Diabetologia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1007\/s12035-016-9684-x","article-title":"Pramlintide Antagonizes Beta Amyloid (A\u03b2)- and Human Amylin-Induced Depression of Hippocampal Long-Term Potentiation","volume":"54","author":"Kimura","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_59","first-page":"345","article-title":"Light, melatonin and the sleep-wake cycle","volume":"19","author":"Brown","year":"1994","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.neuchi.2015.03.002","article-title":"Melatonin: Physiological effects in humans","volume":"61","author":"Claustrat","year":"2015","journal-title":"Neurochirurgie"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Gobetti, R.A.P., Bueno, C., Soster, L.M.S.F.A., Monazzi, A.C.C.B.L., do Amaral, F.G., Capellano, A.M., da Silva, N.S., and Cipolla-Neto, J. (2025). Sleep and Rhythmic Profile After Pineal Gland Removal in Humans. J. Sleep Res., 35.","DOI":"10.1111\/jsr.70171"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/B978-0-12-819975-6.00021-2","article-title":"Melatonin and the circadian system: Keys for health with a focus on sleep","volume":"179","author":"Pevet","year":"2021","journal-title":"Handb. Clin. Neurol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"100678","DOI":"10.37349\/en.2025.100678","article-title":"Melatonin regulation of phase separation in Neuro-PASC: Out-maneuvering Janus-faced amyloids","volume":"4","author":"Loh","year":"2025","journal-title":"Explor. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.neubiorev.2015.04.010","article-title":"Sleep disruption and the sequelae associated with traumatic brain injury","volume":"55","author":"Smith","year":"2015","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1046\/j.1471-4159.2003.01654.x","article-title":"Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer\u2019s disease","volume":"85","author":"Matsubara","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/j.1600-079X.1999.tb00619.x","article-title":"Alzheimer beta protein mediated oxidative damage of mitochondrial DNA: Prevention by melatonin","volume":"27","author":"Pappolla","year":"1999","journal-title":"J. Pineal Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1034\/j.1600-079x.2002.1o838.x","article-title":"The neuroprotective activities of melatonin against the Alzheimer beta-protein are not mediated by melatonin membrane receptors","volume":"32","author":"Pappolla","year":"2002","journal-title":"J. Pineal Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ibneur.2023.01.005","article-title":"Melatonin reduces \u03b2-amyloid accumulation and improves short-term memory in streptozotocin-induced sporadic Alzheimer\u2019s disease model","volume":"14","author":"Andrade","year":"2023","journal-title":"IBRO Neurosci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/978-1-4939-7811-3_5","article-title":"Replica Exchange Molecular Dynamics: A Practical Application Protocol with Solutions to Common Problems and a Peptide Aggregation and Self-Assembly Example","volume":"1777","author":"Qi","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Wang, G., Zhu, X., Song, X., Zhang, Q., and Qian, Z. (2022). Melatonin Inhibits hIAPP Oligomerization by Preventing beta-Sheet and Hydrogen Bond Formation of the Amyloidogenic Region Revealed by Replica-Exchange Molecular Dynamics Simulation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810264"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"14454","DOI":"10.1021\/bi048582a","article-title":"Inhibition of islet amyloid polypeptide fibril formation: A potential role for heteroaromatic interactions","volume":"43","author":"Porat","year":"2004","journal-title":"Biochemistry"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4553","DOI":"10.1007\/s10787-025-01859-y","article-title":"Therapeutic potential of melatonin-induced mitophagy in the pathogenesis of Alzheimer\u2019s disease","volume":"33","author":"Goleij","year":"2025","journal-title":"Inflammopharmacology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"149637","DOI":"10.1016\/j.brainres.2025.149637","article-title":"Melatonin protects mouse hippocampal neurons from neurotoxicity induced by amyloid \u03b2-peptide25-35","volume":"1859","author":"Salgado","year":"2025","journal-title":"Brain Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"10414","DOI":"10.1007\/s12035-025-04904-7","article-title":"Unveiling the Protective Roles of Melatonin on Glial Cells in the Battle Against Alzheimer\u2019s Disease-Insights from In Vivo and In Vitro Studies","volume":"62","author":"Sirimaharaj","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s40035-022-00302-4","article-title":"Melatonin ameliorates tau-related pathology via the miR-504-3p and CDK5 axis in Alzheimer\u2019s disease","volume":"11","author":"Chen","year":"2022","journal-title":"Transl. Neurodegener."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1002\/cbin.70013","article-title":"A Proteomics Profiling Reveals the Neuroprotective Effects of Melatonin on Exogenous \u03b2-amyloid-42 Induced Mitochondrial Impairment, Intracellular \u03b2-amyloid Accumulation and Tau Hyperphosphorylation in Human SH-SY5Y Cells","volume":"49","author":"Panmanee","year":"2025","journal-title":"Cell Biol. Int."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"637","DOI":"10.2174\/1567205015666180411092551","article-title":"Melatonin Treatment Enhances A\u03b2 Lymphatic Clearance in a Transgenic Mouse Model of Amyloidosis","volume":"15","author":"Pappolla","year":"2018","journal-title":"Curr. Alzheimer Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/jphp.12682","article-title":"A review of the protective role of melatonin during phosphine-induced cardiotoxicity: Focus on mitochondrial dysfunction, oxidative stress and apoptosis","volume":"69","author":"Asghari","year":"2017","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Jauhari, A., Monek, A.C., Suofu, Y., Amygdalos, O.R., Singh, T., Baranov, S.V., Carlisle, D.L., and Friedlander, R.M. (2025). Melatonin Deficits Result in Pathologic Metabolic Reprogramming in Differentiated Neurons. J. Pineal Res., 77.","DOI":"10.1111\/jpi.70037"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/j.1600-079X.2010.00747.x","article-title":"Amyloid-beta neurotoxicity in organotypic culture is attenuated by melatonin: Involvement of GSK-3beta, tau and neuroinflammation","volume":"48","author":"Hoppe","year":"2010","journal-title":"J. Pineal Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1111\/jphp.13165","article-title":"Effects of the drug combination memantine and melatonin on impaired memory and brain neuronal deficits in an amyloid-predominant mouse model of Alzheimer\u2019s disease","volume":"71","author":"Zharkovskaja","year":"2019","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Dies, H., Toppozini, L., and Rheinst\u00e4dter, M.C. (2014). The interaction between amyloid-\u03b2 peptides and anionic lipid membranes containing cholesterol and melatonin. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099124"},{"key":"ref_83","first-page":"459806","article-title":"Alterations in Lipid Levels of Mitochondrial Membranes Induced by Amyloid-\u03b2: A Protective Role of Melatonin","volume":"2012","author":"Melnikov","year":"2012","journal-title":"Int. J. Alzheimers Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"6981","DOI":"10.3390\/ijms14046981","article-title":"Melatonin and pancreatic islets: Interrelationships between melatonin, insulin and glucagon","volume":"14","author":"Peschke","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Lauritzen, E.S., Stoy, J., Baech-Laursen, C., Grarup, N., Jessen, N., Hansen, T., Moller, N., Hartmann, B., Holst, J.J., and Kampmann, U. (2021). The Effect of Melatonin on Incretin Hormones: Results from Experimental and Randomized Clinical Studies. J. Clin. Endocrinol. Metab., 106.","DOI":"10.1210\/clinem\/dgab521"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Kampmann, U., Lauritzen, E.S., Grarup, N., Jessen, N., Hansen, T., Moller, N., and Stoy, J. (2021). Acute metabolic effects of melatonin-A randomized crossover study in healthy young men. J. Pineal Res., 70.","DOI":"10.1111\/jpi.12706"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Huang, Y., Dou, X., He, M., Su, Y., Lin, H., and Yang, Y. (2025). The G-allele of rs10830963 in MTNR1B Exerts Stage-Specific Effects Across the Trajectory of Type 2 Diabetes: A Multi-State Analysis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26167855"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.2337\/db15-0999","article-title":"Impact of Common Diabetes Risk Variant in MTNR1B on Sleep, Circadian, and Melatonin Physiology","volume":"65","author":"Lane","year":"2016","journal-title":"Diabetes"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/ng.288","article-title":"Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion","volume":"41","author":"Lyssenko","year":"2009","journal-title":"Nat. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2910\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T05:19:18Z","timestamp":1774415958000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2910"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,23]]},"references-count":89,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27062910"],"URL":"https:\/\/doi.org\/10.3390\/ijms27062910","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,23]]}}}