{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:11:07Z","timestamp":1792213867400,"version":"4.4.0"},"reference-count":91,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hong Kong Research Grant Council","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"The University of Hong Kong (Seed Fund for Basic Research and Seed Fund for Translational &amp; Applied Research)","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease is a neurodegenerative disorder associated with age, and is characterized by pathological markers such as amyloid-beta plaques and neurofibrillary tangles. Symptoms of AD include cognitive impairments, anxiety and depression. It has also been shown that individuals with AD have impaired neurotransmission, which may result from the accumulation of amyloid plaques and neurofibrillary tangles. Preclinical studies showed that melatonin, a monoaminergic neurotransmitter released from the pineal gland, is able to ameliorate AD pathologies and restore cognitive impairments. Theoretically, inhibition of the pathological progression of AD by melatonin treatment should also restore the impaired neurotransmission. This review aims to explore the impact of AD on neurotransmission, and whether and how melatonin can enhance neurotransmission via improving AD pathology.<\/jats:p>","DOI":"10.3390\/ijms22136841","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T11:07:40Z","timestamp":1624619260000},"page":"6841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Regulation of Melatonin and Neurotransmission in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8934-738X","authenticated-orcid":false,"given":"Jaydeep","family":"Roy","sequence":"first","affiliation":[{"name":"School of Biomedical, Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1366-1284","authenticated-orcid":false,"given":"Ka Chun","family":"Tsui","sequence":"additional","affiliation":[{"name":"School of Biomedical, Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonah","family":"Ng","sequence":"additional","affiliation":[{"name":"School of Biomedical, Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man-Lung","family":"Fung","sequence":"additional","affiliation":[{"name":"School of Biomedical, Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6692-6285","authenticated-orcid":false,"given":"Lee Wei","family":"Lim","sequence":"additional","affiliation":[{"name":"School of Biomedical, Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/j.1600-079X.1999.tb00575.x","article-title":"Melatonin affects the metabolism of the \u03b2-amyloid precursor protein in different cell types","volume":"26","author":"Lahiri","year":"1999","journal-title":"J. Pineal Res."},{"key":"ref_2","unstructured":"Alzheimer\u2019s Disease International (2019). World Alzheimer Report 2019, Alzheimer\u2019s Disease International."},{"key":"ref_3","first-page":"1010","article-title":"Mechanisms of Melatonin in Alleviating Alzheimer\u2019s Disease","volume":"15","author":"Mayuri","year":"2017","journal-title":"Curr. Neuropharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e015746","DOI":"10.1136\/bmjopen-2016-015746","article-title":"Signs and symptoms preceding the diagnosis of Alzheimer\u2019s disease: A systematic scoping review of literature from 1937 to 2016","volume":"7","author":"Bature","year":"2017","journal-title":"BMJ Open"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"969","DOI":"10.3233\/JAD-170256","article-title":"A Critical Assessment of Research on Neurotransmitters in Alzheimer\u2019s Disease","volume":"57","author":"Reddy","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1093\/hmg\/ddr139","article-title":"Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer\u2019s disease: Implications for neuronal damage","volume":"20","author":"Manczak","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"McEnery, M.W., and Siegel, R.E. (2014). Neurotransmitter Receptors, Elsevier Inc.. [2nd ed.].","DOI":"10.1016\/B978-0-12-385157-4.00044-0"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/S0166-2236(98)01349-6","article-title":"Tripartite synapses: Glia, the unacknowledged partner","volume":"22","author":"Araque","year":"1999","journal-title":"Trends Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.3233\/JAD-161118","article-title":"Therapeutics of Neurotransmitters in Alzheimer\u2019s Disease","volume":"57","author":"Kandimalla","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.14336\/AD.2019.1125","article-title":"Relationships between mitochondrial dysfunction and neurotransmission failure in Alzheimer\u2019s disease","volume":"11","author":"Wong","year":"2020","journal-title":"Aging Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.pneurobio.2016.04.001","article-title":"Monoaminergic neuropathology in Alzheimer\u2019s disease","volume":"151","author":"Wray","year":"2017","journal-title":"Prog. Neurobiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.pneurobio.2008.04.001","article-title":"Physiological effects of melatonin: Role of melatonin receptors and signal transduction pathways","volume":"85","author":"Pandiperumal","year":"2008","journal-title":"Prog. Neurobiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.ejphar.2010.04.041","article-title":"Effect of melatonin on neuroinflammation and acetylcholinesterase activity induced by LPS in rat brain","volume":"640","author":"Tyagi","year":"2010","journal-title":"Eur. J. Pharm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1046\/j.1365-2826.2001.00656.x","article-title":"Calcium-Dependent Effects of Melatonin Inhibition of Glutamatergic Response in Rat Striatum","volume":"13","author":"Escames","year":"2001","journal-title":"J. Neuroendocr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The Amyloid Hypothesis of Alzheimer\u2019s Disease: Progress and Problems on the Road to Therapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16180","DOI":"10.1523\/JNEUROSCI.3020-14.2014","article-title":"Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury","volume":"34","author":"Iliff","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e40070","DOI":"10.7554\/eLife.40070","article-title":"Aquaporin-4-dependent glymphatic solute transport in the rodent brain","volume":"7","author":"Mestre","year":"2018","journal-title":"eLife"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.cell.2020.03.037","article-title":"Targeting aquaporin-4 subcellular localization to treat central nervous system edema","volume":"181","author":"Kitchen","year":"2020","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"183573","DOI":"10.1016\/j.bbamem.2021.183573","article-title":"The effects of trifluoperazine on brain edema, aquaporin-4 expression and metabolic markers during the acute phase of stroke using photothrombotic mouse model","volume":"1863","author":"Sylvain","year":"2021","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"16755","DOI":"10.1523\/JNEUROSCI.4521-10.2010","article-title":"Reimagining Alzheimer\u2019s Disease--An Age-Based Hypothesis","volume":"30","author":"Herrup","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1212\/01.wnl.0000311269.57716.63","article-title":"Protective effects of NSAIDs on the development of Alzheimer disease","volume":"70","author":"Vlad","year":"2008","journal-title":"Neurology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1523\/JNEUROSCI.23-07-02557.2003","article-title":"Neuronal Cell Death Is Preceded by Cell Cycle Events at All Stages of Alzheimer\u2019s Disease","volume":"23","author":"Yang","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2174\/1570159X13666150716165726","article-title":"Alzheimer\u2019s disease: Targeting the Cholinergic System","volume":"14","author":"Talita","year":"2016","journal-title":"Curr. Neuropharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.1365-2990.1978.tb00545.x","article-title":"Changes in brain cholinesterases in senile dementia of Alzheimer type","volume":"4","author":"Perry","year":"1978","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1093\/brain\/awy132","article-title":"The cholinergic system in the pathophysiology and treatment of Alzheimer\u2019s disease","volume":"141","author":"Hampel","year":"2018","journal-title":"Brain"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3234","DOI":"10.1523\/JNEUROSCI.22-08-03234.2002","article-title":"Cholinergic changes in the APP23 transgenic mouse model of cerebral amyloidosis","volume":"22","author":"Boncristiano","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.neuint.2004.11.005","article-title":"Analysis of cholinergic markers, biogenic amines, and amino acids in the CNS of two APP overexpression mouse models","volume":"46","author":"Marescau","year":"2005","journal-title":"Neurochem. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.nbd.2010.10.002","article-title":"Cholinotrophic basal forebrain system alterations in 3xTg-AD transgenic mice","volume":"41","author":"Perez","year":"2011","journal-title":"Neurobiol. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1016\/j.neuroscience.2009.09.024","article-title":"Amyloid-\u03b2 expression in retrosplenial cortex of triple transgenic mice: Relationship to cholinergic axonal afferents from medial septum","volume":"164","author":"Robertson","year":"2009","journal-title":"Neuroscience"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.brainres.2008.10.029","article-title":"Decreased acetylcholine release is correlated to memory impairment in the Tg2576 transgenic mouse model of Alzheimer\u2019s disease","volume":"1249","author":"Watanabe","year":"2008","journal-title":"Brain Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.nbd.2006.03.012","article-title":"Cholinergic dysfunction, neuronal damage and axonal loss in TgCRND8 mice","volume":"23","author":"Bellucci","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/cne.10737","article-title":"Cholinergic neuropathology in a mouse model of Alzheimer\u2019s disease","volume":"462","author":"German","year":"2003","journal-title":"J. Comp. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1172\/JCI27120","article-title":"Cholinergic dysfunction in a mouse model of Alzheimer disease is reversed by an anti-A\u03b2 antibody","volume":"116","author":"Bales","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1097\/NEN.0b013e318288a8dd","article-title":"Rapid \u03b2-Amyloid Deposition and Cognitive Impairment After Cholinergic Denervation in APP\/PS1 Mice","volume":"72","author":"Thyssen","year":"2013","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Govindpani, K., Calvo-Flores Guzm\u00e1n, B., Vinnakota, C., Waldvogel, H.J., Faull, R.L., and Kwakowsky, A. (2017). Towards a Better Understanding of GABAergic Remodeling in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081813"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1038\/nm.3639","article-title":"GABA from reactive astrocytes impairs memory in mouse models of Alzheimer\u2019s disease","volume":"20","author":"Jo","year":"2014","journal-title":"Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"765","DOI":"10.3233\/JAD-2011-111502","article-title":"Impaired glutamatergic and GABAergic function at early age in A\u03b2PPswe-PS1dE9 mice: Implications for Alzheimer\u2019s disease","volume":"28","author":"Tiwari","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.neuint.2010.04.001","article-title":"A metabolomic study of the CRND8 transgenic mouse model of Alzheimer\u2019s disease","volume":"56","author":"Salek","year":"2010","journal-title":"Neurochem. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3233\/ADR-170003","article-title":"The GABA-Working Memory Relationship in Alzheimer\u2019s Disease","volume":"1","author":"Mandal","year":"2017","journal-title":"J. Alzheimers Dis. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"641","DOI":"10.2165\/00023210-200317090-00004","article-title":"The Glutamatergic System and Alzheimer\u2019s Disease: Therapeutic Implications","volume":"17","author":"Butterfield","year":"2003","journal-title":"CNS Drugs"},{"key":"ref_41","first-page":"3","article-title":"Neuropathologic changes in Alzheimer\u2019s disease: Potential targets for treatment","volume":"67","author":"Wenk","year":"2006","journal-title":"J. Clin. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"105402","DOI":"10.1016\/j.nbd.2021.105402","article-title":"Tyrosine phosphatase PTP1B impairs presynaptic NMDA receptor-mediated plasticity in a mouse model of Alzheimer\u2019s disease","volume":"156","author":"Zhang","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.neurobiolaging.2014.09.006","article-title":"A\u03b2 and NMDAR activation cause mitochondrial dysfunction involving ER calcium release","volume":"36","author":"Ferreira","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.3233\/JAD-160763","article-title":"Role of glutamate and NMDA receptors in Alzheimer\u2019s disease","volume":"57","author":"Wang","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nrn2911","article-title":"Synaptic versus extrasynaptic NMDA receptor signalling: Implications for neurodegenerative disorders","volume":"11","author":"Hardingham","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1177\/1073858408322675","article-title":"Presynaptic NMDA receptors: Newly appreciated roles in cortical synaptic function and plasticity","volume":"14","author":"Corlew","year":"2008","journal-title":"Neuroscientist"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1007\/s10072-016-2546-5","article-title":"Dysfunction of NMDA receptors in Alzheimer\u2019s disease","volume":"37","author":"Zhang","year":"2016","journal-title":"Neurol. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.nbd.2003.12.006","article-title":"\u03b2-Amyloid25-35 inhibits glutamate uptake in cultured neurons and astrocytes: Modulation of uptake as a survival mechanism","volume":"15","author":"Brera","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"E2518","DOI":"10.1073\/pnas.1306832110","article-title":"A\u03b2 induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss","volume":"110","author":"Talantova","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1038\/nn1503","article-title":"Regulation of NMDA receptor trafficking by amyloid-\u03b2","volume":"8","author":"Snyder","year":"2005","journal-title":"Nat. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"771","DOI":"10.3233\/JAD-142160","article-title":"Altered neurotransmission prior to cognitive decline in A\u03b2PP\/PS1 mice, a model of Alzheimer\u2019s disease","volume":"44","author":"Hascup","year":"2015","journal-title":"J. Alzheimers Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.nbd.2004.09.005","article-title":"Altered metabolic profile in the frontal cortex of PS2APP transgenic mice, monitored throughout their life span","volume":"18","author":"Metzger","year":"2005","journal-title":"Neurobiol. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.brainres.2010.09.072","article-title":"Altered distribution of mGlu2 receptors in \u03b2-amyloid-affected brain regions of Alzheimer cases and aged PS2APP mice","volume":"1363","author":"Richards","year":"2010","journal-title":"Brain Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.nbd.2014.11.017","article-title":"Altered GluN2B NMDA receptor function and synaptic plasticity during early pathology in the PS2APP mouse model of Alzheimer\u2019s disease","volume":"74","author":"Hanson","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1002\/cne.23536","article-title":"Early fear memory defects are associated with altered synaptic plasticity and molecular architecture in the TgCRND8 Alzheimer\u2019s disease mouse model","volume":"522","author":"Steele","year":"2014","journal-title":"J. Comp. Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"158","DOI":"10.2174\/156720510790691173","article-title":"Genetic susceptibility to behavioural and psychological symptoms in Alzheimer disease","volume":"7","author":"Borroni","year":"2010","journal-title":"Curr. Alzheimer Res"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"13805","DOI":"10.1523\/JNEUROSCI.4218-08.2008","article-title":"Amyloid Pathology Is Associated with Progressive Monoaminergic Neurodegeneration in a Transgenic Mouse Model of Alzheimer\u2019s Disease","volume":"28","author":"Liu","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"12106","DOI":"10.1523\/JNEUROSCI.1269-16.2016","article-title":"Cross Talk Between Brain Innate Immunity and Serotonin Signaling Underlies Depressive-Like Behavior Induced by Alzheimer\u2019s Amyloid- Oligomers in Mice","volume":"36","author":"Ledo","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.3233\/JAD-2010-100117","article-title":"Plaque Deposition Dependent Decrease in 5-HT2A Serotonin Receptor in A\u03b2PPswe\/PS1dE9 Amyloid Overexpressing Mice","volume":"20","author":"Holm","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/0006-8993(87)91408-9","article-title":"Monoaminergic innervation of the frontal and temporal lobes in Alzheimer\u2019s disease","volume":"401","author":"Palmer","year":"1987","journal-title":"Brain Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"150ra122","DOI":"10.1126\/scitranslmed.3004291","article-title":"Disruption of the sleep-wake cycle and diurnal fluctuation of \u03b2-amyloid in mice with Alzheimer\u2019s disease pathology","volume":"4","author":"Roh","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_62","first-page":"1","article-title":"Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons","volume":"232","author":"Dahlstroem","year":"1964","journal-title":"Acta Physiol. Scand. Suppl."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/0304-3940(95)12256-7","article-title":"Monoaminergic neurotransmitters, their precursors and metabolites in brains of Alzheimer patients","volume":"203","author":"Storga","year":"1996","journal-title":"Neurosci. Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.neurobiolaging.2007.11.010","article-title":"Levodopa ameliorates learning and memory deficits in a murine model of Alzheimer\u2019s disease","volume":"30","author":"Richter","year":"2009","journal-title":"Neurobiol. Aging"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3233\/JAD-181246","article-title":"Loss of Midbrain Dopamine Neurons and Altered Apomorphine EEG Effects in the 5xFAD Mouse Model of Alzheimer\u2019s Disease","volume":"70","author":"Vorobyov","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.nbd.2018.05.006","article-title":"Dopamine loss alters the hippocampus-nucleus accumbens synaptic transmission in the Tg2576 mouse model of Alzheimer\u2019s disease","volume":"116","author":"Cordella","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/nyas.14436","article-title":"Therapeutic potential of neurogenesis and melatonin regulation in Alzheimer\u2019s disease","volume":"1478","author":"Mihardja","year":"2020","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7185","DOI":"10.1074\/jbc.273.13.7185","article-title":"Inhibition of Alzheimer \u03b2-Fibrillogenesis by Melatonin","volume":"273","author":"Pappolla","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/j.1600-079X.2011.00937.x","article-title":"Alzheimer\u2019s disease: Pathological mechanisms and the beneficial role of melatonin","volume":"52","author":"Boga","year":"2012","journal-title":"J. Pineal Res."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"O\u2019Neal-Moffitt, G., Delic, V., Bradshaw, P.C., and Olcese, J. (2015). Prophylactic melatonin significantly reduces Alzheimer\u2019s neuropathology and associated cognitive deficits independent of antioxidant pathways in A\u03b2PPswe\/PS1 mice. Mol. Neurodegener., 10.","DOI":"10.1186\/s13024-015-0027-6"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/j.1600-079X.2009.00692.x","article-title":"Protection against cognitive deficits and markers of neurodegeneration by long-term oral administration of melatonin in a transgenic model of Alzheimer disease","volume":"47","author":"Olcese","year":"2009","journal-title":"J. Pineal Res."},{"key":"ref_72","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_73","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.brainres.2005.01.023","article-title":"Chronic melatonin therapy fails to alter amyloid burden or oxidative damage in old Tg2576 mice: Implications for clinical trials","volume":"1037","author":"Quinn","year":"2005","journal-title":"Brain Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"480","DOI":"10.3389\/fendo.2019.00480","article-title":"Melatonin: Clinical perspectives in neurodegeneration","volume":"10","author":"Cardinali","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_75","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_76","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ejphar.2005.01.023","article-title":"Effect of melatonin on calyculin A-induced tau hyperphosphorylation","volume":"510","author":"Li","year":"2005","journal-title":"Eur. J. Pharm."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1111\/j.1745-7254.2005.00102.x","article-title":"Effects of melatonin on wortmannin-induced tau hyperphosphorylation","volume":"26","author":"Deng","year":"2005","journal-title":"Acta Pharm. Sin."},{"key":"ref_78","first-page":"1124.e1113","article-title":"Melatonin plus physical exercise are highly neuroprotective in the 3xTg-AD mouse","volume":"33","author":"Venegas","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/jphp.12830","article-title":"Melatonin ameliorates A\u03b21-42-induced Alzheimer\u2019s cognitive deficits in mouse model","volume":"70","author":"Gong","year":"2018","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1600-079X.2004.00136.x","article-title":"Effect of inhibiting melatonin biosynthesis on spatial memory retention and tau phosphorylation in rat","volume":"37","author":"Zhu","year":"2004","journal-title":"J. Pineal Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/j.1600-079X.2004.00144.x","article-title":"Melatonin alleviates behavioral deficits associated with apoptosis and cholinergic system dysfunction in the APP 695 transgenic mouse model of Alzheimer\u2019s disease","volume":"37","author":"Feng","year":"2004","journal-title":"J. Pineal Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"113100","DOI":"10.1016\/j.bbr.2020.113100","article-title":"Effects of melatonin and resveratrol on recognition memory and passive avoidance performance in a mouse model of Alzheimer\u2019s disease","volume":"402","author":"Labban","year":"2021","journal-title":"Behav. Brain Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"911","DOI":"10.3233\/JAD-171178","article-title":"Melatonin in Synaptic Impairments of Alzheimer\u2019s Disease","volume":"63","author":"Shi","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e22430","DOI":"10.1002\/jbt.22430","article-title":"Melatonin and its metabolite N (1)-acetyl-N (1)-formyl-5-methoxykynuramine improve learning and memory impairment related to Alzheimer\u2019s disease in rats","volume":"34","author":"Rong","year":"2020","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.ejmech.2015.08.052","article-title":"New multifunctional melatonin-derived benzylpyridinium bromides with potent cholinergic, antioxidant, and neuroprotective properties as innovative drugs for Alzheimer\u2019s disease","volume":"103","author":"Luo","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1007\/s11064-007-9563-y","article-title":"Effect of melatonin and melatonylvalpromide on \u03b2-amyloid and neurofilaments in N2a cells","volume":"33","author":"Wang","year":"2008","journal-title":"Neurochem. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1021\/cn5002073","article-title":"The Melatonin\u2013N, N-Dibenzyl (N-methyl) amine Hybrid ITH91\/IQM157 Affords Neuroprotection in an in Vitro Alzheimer\u2019s Model via Hemo-oxygenase-1 Induction","volume":"6","author":"Buendia","year":"2015","journal-title":"ACS Chem. Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yhbeh.2013.04.009","article-title":"A novel melatonin agonist Neu-P11 facilitates memory performance and improves cognitive impairment in a rat model of Alzheimer\u2019disease","volume":"64","author":"He","year":"2013","journal-title":"Horm. Behav."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"387","DOI":"10.2147\/DDDT.S182684","article-title":"Melatonin receptor stimulation by agomelatine prevents A\u03b2-induced tau phosphorylation and oxidative damage in PC12 cells","volume":"13","author":"Yao","year":"2019","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Aldewachi, H., Al-Zidan, R.N., Conner, M.T., and Salman, M.M. (2021). High-Throughput Screening Platforms in the Discovery of Novel Drugs for Neurodegenerative Diseases. Bioengineering, 8.","DOI":"10.3390\/bioengineering8020030"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Salman, M.M., Al-Obaidi, Z., Kitchen, P., Loreto, A., Bill, R.M., and Wade-Martins, R. (2021). Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094688"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/13\/6841\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:24:02Z","timestamp":1760163842000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/13\/6841"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,25]]},"references-count":91,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["ijms22136841"],"URL":"https:\/\/doi.org\/10.3390\/ijms22136841","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,25]]}}}