{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T17:25:42Z","timestamp":1787678742043,"version":"build-2784847793"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001427","name":"All India Council for Technical Education","doi-asserted-by":"publisher","award":["RPS-NDF 8-35\/RIFD\/RPS-NDF\/POLICY-1\/2018-19"],"award-info":[{"award-number":["RPS-NDF 8-35\/RIFD\/RPS-NDF\/POLICY-1\/2018-19"]}],"id":[{"id":"10.13039\/501100001427","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Manipal Academy of Higher Education, Manipal"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Divers"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Wnt signaling pathway is an evolutionarily conserved pathway responsible for neurogenesis, axon outgrowth, neuronal polarity, synapse formation, and maintenance. Downregulation of Wnt signaling has been found in patients with Alzheimer\u2019s disease (AD). Several experimental approaches to activate Wnt signaling pathway have proven to be beneficial in alleviating AD, which is one of the new therapeutic approaches for AD. The current study focuses on the computational structure-based virtual screening followed by the identification of potential phytomolecules targeting different markers of Wnt signaling like WIF1, DKK1, LRP6, GSK-3\u03b2, and acetylcholine esterase. Initially, screening of 1924 compounds from the plant-based library of Zinc database was done for the selected five proteins using docking approach followed by MM-GBSA calculations. The top five hit molecules were identified for each protein. Based on docking score, and binding interactions, the top two hit molecules for each protein were selected as promising molecules for the molecular dynamic (MD) simulation study with the five proteins. Therefore, from this in silico based study, we report that Mangiferin could be a potential molecule targeting Wnt signaling pathway modulating the LRP6 activity, Baicalin for AChE activity, Chebulic acid for DKK1, ZINC103539689 for WIF1, and Morin for GSk-3\u03b2 protein. However, further validation of the activity is warranted based on in vivo and in vitro experiments for better understanding and strong claim. This study provides an in silico approach for the identification of modulators of the Wnt signaling pathway as a new therapeutic approach for AD.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s11030-022-10395-8","type":"journal-article","created":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T22:02:31Z","timestamp":1644530551000},"page":"2793-2811","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Molecular dynamics and structure-based virtual screening and identification of natural compounds as Wnt signaling modulators: possible therapeutics for Alzheimer\u2019s disease"],"prefix":"10.1007","volume":"26","author":[{"given":"Suman","family":"Manandhar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runali","family":"Sankhe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keerthi","family":"Priya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gangadhar","family":"Hari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harish","family":"Kumar B.","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chetan H.","family":"Mehta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usha Y.","family":"Nayak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2017-9533","authenticated-orcid":false,"given":"K. Sreedhara Ranganath","family":"Pai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,2,11]]},"reference":[{"key":"10395_CR1","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/0092-8674(91)90633-A","volume":"64","author":"R Nusse","year":"1991","unstructured":"Nusse R, Brown A, Papkoff J et al (1991) A new nomenclature for int-1 and related genes: the Wnt gene family. Cell 64:231. https:\/\/doi.org\/10.1016\/0092-8674(91)90633-A","journal-title":"Cell"},{"key":"10395_CR2","doi-asserted-by":"publisher","first-page":"a007864","DOI":"10.1101\/cshperspect.a007864","volume":"4","author":"K Willert","year":"2012","unstructured":"Willert K, Nusse R (2012) Wnt proteins. Cold Spring Harb Perspect Biol 4:a007864\u2013a007864. https:\/\/doi.org\/10.1101\/cshperspect.a007864","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"10395_CR3","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/1750-1326-3-9","volume":"3","author":"NC Inestrosa","year":"2008","unstructured":"Inestrosa NC, Toledo EM (2008) The role of wnt signaling in neuronal dysfunction in Alzheimer\u2019s Disease. Mol Neurodegener 3:9. https:\/\/doi.org\/10.1186\/1750-1326-3-9","journal-title":"Mol Neurodegener"},{"key":"10395_CR4","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/nrn1665","volume":"6","author":"L Ciani","year":"2005","unstructured":"Ciani L, Salinas PC (2005) WNTS in the vertebrate nervous system: from patterning to neuronal connectivity: signalling in neural development. Nat Rev Neurosci 6:351\u2013362. https:\/\/doi.org\/10.1038\/nrn1665","journal-title":"Nat Rev Neurosci"},{"key":"10395_CR5","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1146\/annurev.pharmtox.44.101802.121631","volume":"44","author":"DC Lie","year":"2004","unstructured":"Lie DC, Song H, Colamarino SA et al (2004) Neurogenesis in the adult brain: new strategies for central nervous system diseases. Annu Rev Pharmacol Toxicol 44:399\u2013421. https:\/\/doi.org\/10.1146\/annurev.pharmtox.44.101802.121631","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"10395_CR6","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1038\/nature04108","volume":"437","author":"DC Lie","year":"2005","unstructured":"Lie DC, Colamarino SA, Song HJ et al (2005) Wnt signalling regulates adult hippocampal neurogenesis. Nature 437:1370\u20131375. https:\/\/doi.org\/10.1038\/nature04108","journal-title":"Nature"},{"key":"10395_CR7","first-page":"578","volume":"8","author":"L Wang","year":"2015","unstructured":"Wang L, Liu Y, Li S et al (2015) Wnt signaling pathway participates in valproic acid-induced neuronal differentiation of neural stem cells. Int J Clin Exp Pathol 8:578\u2013585","journal-title":"Int J Clin Exp Pathol"},{"key":"10395_CR8","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1159\/000092097","volume":"3","author":"C Lange","year":"2006","unstructured":"Lange C, Mix E, Rateitschak K, Rolfs A (2006) Wnt signal pathways and neural stem cell differentiation. Neurodegener Dis 3:76\u201386. https:\/\/doi.org\/10.1159\/000092097","journal-title":"Neurodegener Dis"},{"key":"10395_CR9","doi-asserted-by":"publisher","first-page":"2401","DOI":"10.1007\/s11064-008-9710-0","volume":"33","author":"F Caraci","year":"2008","unstructured":"Caraci F, Busceti C, Biagioni F et al (2008) The Wnt antagonist, Dickkopf-1, as a target for the treatment of neurodegenerative disorders. Neurochem Res 33:2401\u20132406. https:\/\/doi.org\/10.1007\/s11064-008-9710-0","journal-title":"Neurochem Res"},{"key":"10395_CR10","doi-asserted-by":"publisher","first-page":"21427","DOI":"10.1074\/jbc.M800014200","volume":"283","author":"MV Sem\u00ebnov","year":"2008","unstructured":"Sem\u00ebnov MV, Zhang X, He X (2008) DKK1 antagonizes Wnt signaling without promotion of LRP6 internalization and degradation. J Biol Chem 283:21427\u201321432. https:\/\/doi.org\/10.1074\/jbc.M800014200","journal-title":"J Biol Chem"},{"key":"10395_CR11","doi-asserted-by":"publisher","first-page":"22429","DOI":"10.1074\/jbc.R600015200","volume":"281","author":"MD Gordon","year":"2006","unstructured":"Gordon MD, Nusse R (2006) Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors. J Biol Chem 281:22429\u201322433. https:\/\/doi.org\/10.1074\/jbc.R600015200","journal-title":"J Biol Chem"},{"key":"10395_CR12","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/S0165-6147(03)00100-7","volume":"24","author":"A Caricasole","year":"2003","unstructured":"Caricasole A, Copani A, Caruso A et al (2003) The wnt pathway, cell-cycle activation and \u03b2-amyloid: novel therapeutic strategies in Alzheimer\u2019s disease? Trends Pharmacol Sci 24:233\u2013238. https:\/\/doi.org\/10.1016\/S0165-6147(03)00100-7","journal-title":"Trends Pharmacol Sci"},{"key":"10395_CR13","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1089\/zeb.2016.1319","volume":"14","author":"FT Lim","year":"2017","unstructured":"Lim FT, Ogawa S, Smith AI, Parhar IS (2017) Proteomics identification of potential candidates involved in cell proliferation for early stage of brain regeneration in the adult zebrafish. Zebrafish 14:10\u201322. https:\/\/doi.org\/10.1089\/zeb.2016.1319","journal-title":"Zebrafish"},{"key":"10395_CR14","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1007\/s12035-018-1103-z","volume":"56","author":"J Folke","year":"2019","unstructured":"Folke J, Pakkenberg B, Brudek T (2019) Impaired wnt signaling in the prefrontal cortex of Alzheimer\u2019s disease. Mol Neurobiol 56:873\u2013891. https:\/\/doi.org\/10.1007\/s12035-018-1103-z","journal-title":"Mol Neurobiol"},{"key":"10395_CR15","doi-asserted-by":"publisher","first-page":"6021","DOI":"10.1523\/JNEUROSCI.1381-04.2004","volume":"24","author":"A Caricasole","year":"2004","unstructured":"Caricasole A, Copani A, Caraci F et al (2004) Induction of Dickkopf-1, a negative modulator of the Wnt pathway, is associated with neuronal degeneration in Alzheimer\u2019s brain. J Neurosci 24:6021\u20136027. https:\/\/doi.org\/10.1523\/JNEUROSCI.1381-04.2004","journal-title":"J Neurosci"},{"key":"10395_CR16","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.yexcr.2004.02.028","volume":"297","author":"AR Alvarez","year":"2004","unstructured":"Alvarez AR, Godoy JA, Mullendorff K et al (2004) Wnt-3a overcomes \u03b2-amyloid toxicity in rat hippocampal neurons. Exp Cell Res 297:186\u2013196. https:\/\/doi.org\/10.1016\/j.yexcr.2004.02.028","journal-title":"Exp Cell Res"},{"key":"10395_CR17","doi-asserted-by":"publisher","first-page":"9172","DOI":"10.1074\/jbc.M109.092130","volume":"285","author":"E Bourhis","year":"2010","unstructured":"Bourhis E, Tam C, Franke Y et al (2010) Reconstitution of a frizzled8\u00b7Wnt3a\u00b7LRP6 signaling complex reveals multiple Wnt and Dkk1 binding sites on LRP6. J Biol Chem 285:9172\u20139179. https:\/\/doi.org\/10.1074\/jbc.M109.092130","journal-title":"J Biol Chem"},{"key":"10395_CR18","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s10989-017-9589-1","volume":"24","author":"E Rismani","year":"2018","unstructured":"Rismani E, Rahimi H, Arab SS et al (2018) Computationally design of inhibitory peptides against wnt signaling pathway. In silico insight on complex of DKK1 and LRP6. Int J Pept Res Ther 24:49\u201360. https:\/\/doi.org\/10.1007\/s10989-017-9589-1","journal-title":"Int J Pept Res Ther"},{"key":"10395_CR19","doi-asserted-by":"publisher","first-page":"2074","DOI":"10.1002\/cmdc.201700551","volume":"12","author":"S Brogi","year":"2017","unstructured":"Brogi S, Maramai S, Brindisi M et al (2017) Activation of the wnt pathway by small peptides: rational design, synthesis and biological evaluation. ChemMedChem 12:2074\u20132085. https:\/\/doi.org\/10.1002\/cmdc.201700551","journal-title":"ChemMedChem"},{"key":"10395_CR20","doi-asserted-by":"publisher","first-page":"129073","DOI":"10.1016\/j.molstruc.2020.129073","volume":"1224","author":"R Sankhe","year":"2021","unstructured":"Sankhe R, Rathi E, Manandhar S et al (2021) Repurposing of existing FDA approved drugs for Neprilysin inhibition: an in-silico study. J Mol Struct 1224:129073. https:\/\/doi.org\/10.1016\/j.molstruc.2020.129073","journal-title":"J Mol Struct"},{"key":"10395_CR21","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.3390\/ijms19061578","volume":"19","author":"N Thomford","year":"2018","unstructured":"Thomford N, Senthebane D, Rowe A et al (2018) Natural products for drug discovery in the 21st century: innovations for novel drug discovery. Int J Mol Sci 19:1578. https:\/\/doi.org\/10.3390\/ijms19061578","journal-title":"Int J Mol Sci"},{"key":"10395_CR22","doi-asserted-by":"publisher","first-page":"162","DOI":"10.5958\/0975-4385","volume":"1","author":"K Tripathi","year":"2009","unstructured":"Tripathi K (2009) Curcumin-the spice of life-II. Res J Pharmacogn Phytochem 1:162\u2013168. https:\/\/doi.org\/10.5958\/0975-4385","journal-title":"Res J Pharmacogn Phytochem"},{"key":"10395_CR23","doi-asserted-by":"publisher","first-page":"3852","DOI":"10.3390\/molecules25173852","volume":"25","author":"M Santana de Oliveira","year":"2020","unstructured":"Santana de Oliveira M, Neves da Cruz J, Almeida da Costa W et al (2020) Chemical composition, antimicrobial properties of siparuna guianensis essential oil and a molecular docking and dynamics molecular study of its major chemical constituent. Molecules 25:3852. https:\/\/doi.org\/10.3390\/molecules25173852","journal-title":"Molecules"},{"key":"10395_CR24","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.toxicon.2021.02.015","volume":"195","author":"OS da Silva J\u00fanior","year":"2021","unstructured":"da Silva J\u00fanior OS, de Franco CJP, de Moraes AAB et al (2021) In silico analyses of toxicity of the major constituents of essential oils from two Ipomoea L. species. Toxicon 195:111\u2013118. https:\/\/doi.org\/10.1016\/j.toxicon.2021.02.015","journal-title":"Toxicon"},{"key":"10395_CR25","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1038\/nsmb.2081","volume":"18","author":"T Malinauskas","year":"2011","unstructured":"Malinauskas T, Aricescu AR, Lu W et al (2011) Modular mechanism of Wnt signaling inhibition by Wnt inhibitory factor 1. Nat Struct Mol Biol 18:886\u2013893. https:\/\/doi.org\/10.1038\/nsmb.2081","journal-title":"Nat Struct Mol Biol"},{"key":"10395_CR26","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.devcel.2011.09.003","volume":"21","author":"VE Ahn","year":"2011","unstructured":"Ahn VE, Chu MLH, Choi HJ et al (2011) Structural basis of Wnt signaling inhibition by dickkopf binding to LRP5\/6. Dev Cell 21:862\u2013873. https:\/\/doi.org\/10.1016\/j.devcel.2011.09.003","journal-title":"Dev Cell"},{"key":"10395_CR27","doi-asserted-by":"publisher","first-page":"45937","DOI":"10.1074\/jbc.M306268200","volume":"278","author":"R Bhat","year":"2003","unstructured":"Bhat R, Xue Y, Berg S et al (2003) Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. J Biol Chem 278:45937\u201345945. https:\/\/doi.org\/10.1074\/jbc.M306268200","journal-title":"J Biol Chem"},{"key":"10395_CR28","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1021\/ml400304w","volume":"4","author":"J Cheung","year":"2013","unstructured":"Cheung J, Gary EN, Shiomi K, Rosenberry TL (2013) Structures of human acetylcholinesterase bound to dihydrotanshinone i and territrem B show peripheral site flexibility. ACS Med Chem Lett 4:1091\u20131096. https:\/\/doi.org\/10.1021\/ml400304w","journal-title":"ACS Med Chem Lett"},{"key":"10395_CR29","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1016\/J.BBADIS.2013.06.012","volume":"1832","author":"PH R,","year":"2013","unstructured":"PH R, (2013) Amyloid beta-induced glycogen synthase kinase 3\u03b2 phosphorylated VDAC1 in Alzheimer\u2019s disease: implications for synaptic dysfunction and neuronal damage. Biochim Biophys Acta 1832:1913\u20131921. https:\/\/doi.org\/10.1016\/J.BBADIS.2013.06.012","journal-title":"Biochim Biophys Acta"},{"key":"10395_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-21256-6","volume":"8","author":"H Liu","year":"2018","unstructured":"Liu H, Luo K, Luo D (2018) Guanosine monophosphate reductase 1 is a potential therapeutic target for Alzheimer\u2019s disease. Sci Rep 8:1\u201310. https:\/\/doi.org\/10.1038\/s41598-018-21256-6","journal-title":"Sci Rep"},{"key":"10395_CR31","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1021\/jm0306430","volume":"47","author":"RA Friesner","year":"2004","unstructured":"Friesner RA, Banks JL, Murphy RB et al (2004) Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 47:1739\u20131749. https:\/\/doi.org\/10.1021\/jm0306430","journal-title":"J Med Chem"},{"key":"10395_CR32","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1021\/ci800324m","volume":"49","author":"TA Halgren","year":"2009","unstructured":"Halgren TA (2009) Identifying and characterizing binding sites and assessing druggability. J Chem Inf Model 49:377\u2013389. https:\/\/doi.org\/10.1021\/ci800324m","journal-title":"J Chem Inf Model"},{"key":"10395_CR33","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1021\/ci049714+","volume":"45","author":"JJ Irwin","year":"2005","unstructured":"Irwin JJ, Shoichet BK (2005) ZINC\u2013a free database of commercially available compounds for virtual screening. J Chem Inf Model 45:177\u2013182. https:\/\/doi.org\/10.1021\/ci049714+","journal-title":"J Chem Inf Model"},{"key":"10395_CR34","doi-asserted-by":"publisher","first-page":"129396","DOI":"10.1016\/j.molstruc.2020.129396","volume":"1226","author":"B Manasa","year":"2021","unstructured":"Manasa B, Manandhar S, Hari G et al (2021) Virtual structure-based docking, WaterMap, and molecular dynamics guided identification of the potential natural compounds as inhibitors of protein-tyrosine phosphatase 1B. J Mol Struct 1226:129396. https:\/\/doi.org\/10.1016\/j.molstruc.2020.129396","journal-title":"J Mol Struct"},{"key":"10395_CR35","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","volume":"10","author":"S Genheden","year":"2015","unstructured":"Genheden S, Ryde U (2015) The MM\/PBSA and MM\/GBSA methods to estimate ligand-binding affinities. Expert Opin Drug Discov 10:449\u2013461. https:\/\/doi.org\/10.1517\/17460441.2015.1032936","journal-title":"Expert Opin Drug Discov"},{"key":"10395_CR36","doi-asserted-by":"publisher","first-page":"3115","DOI":"10.1080\/07391102.2020.1761878","volume":"39","author":"CBR Santos","year":"2021","unstructured":"Santos CBR, Santos KLB, Cruz JN et al (2021) Molecular modeling approaches of selective adenosine receptor type 2A agonists as potential anti-inflammatory drugs. J Biomol Struct Dyn 39:3115\u20133127. https:\/\/doi.org\/10.1080\/07391102.2020.1761878","journal-title":"J Biomol Struct Dyn"},{"key":"10395_CR37","doi-asserted-by":"publisher","first-page":"4183","DOI":"10.3390\/molecules25184183","volume":"25","author":"PHF Ara\u00fajo","year":"2020","unstructured":"Ara\u00fajo PHF, Ramos RS, da Cruz JN et al (2020) Identification of potential COX-2 inhibitors for the treatment of inflammatory diseases using molecular modeling approaches. Molecules 25:4183. https:\/\/doi.org\/10.3390\/molecules25184183","journal-title":"Molecules"},{"key":"10395_CR38","doi-asserted-by":"publisher","first-page":"2794","DOI":"10.1002\/prot.23106","volume":"79","author":"J Li","year":"2011","unstructured":"Li J, Abel R, Zhu K et al (2011) The VSGB 2.0 model: a next generation energy model for high resolution protein structure modeling. Proteins Struct Funct Bioinform 79:2794\u20132812. https:\/\/doi.org\/10.1002\/prot.23106","journal-title":"Proteins Struct Funct Bioinform"},{"key":"10395_CR39","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1002\/qsar.200730051","volume":"27","author":"L Ioakimidis","year":"2008","unstructured":"Ioakimidis L, Thoukydidis L, Mirza A et al (2008) Benchmarking the reliability of QikProp. Correlation between experimental and predicted values. QSAR Comb Sci 27:445\u2013456. https:\/\/doi.org\/10.1002\/qsar.200730051","journal-title":"QSAR Comb Sci"},{"key":"10395_CR40","doi-asserted-by":"publisher","first-page":"10282","DOI":"10.1021\/JM300871X","volume":"55","author":"J Cheung","year":"2012","unstructured":"Cheung J, Rudolph MJ, Burshteyn F et al (2012) Structures of human acetylcholinesterase in complex with pharmacologically important ligands. J Med Chem 55:10282\u201310286. https:\/\/doi.org\/10.1021\/JM300871X","journal-title":"J Med Chem"},{"key":"10395_CR41","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1038\/nsmb.2139","volume":"18","author":"Z Cheng","year":"2011","unstructured":"Cheng Z, Biechele T, Wei Z et al (2011) Crystal structures of the extracellular domain of LRP6 and its complex with DKK1. Nat Struct Mol Biol 18:1204\u20131210. https:\/\/doi.org\/10.1038\/nsmb.2139","journal-title":"Nat Struct Mol Biol"},{"key":"10395_CR42","doi-asserted-by":"publisher","first-page":"pe22","DOI":"10.1126\/scisignal.2003028","volume":"5","author":"J Bao","year":"2012","unstructured":"Bao J, Zheng JJ, Wu D (2012) The structural basis of DKK-mediated inhibition of Wnt\/LRP signaling. Sci Signal 5:pe22. https:\/\/doi.org\/10.1126\/scisignal.2003028","journal-title":"Sci Signal"},{"key":"10395_CR43","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1016\/j.devcel.2011.09.007","volume":"21","author":"S Chen","year":"2011","unstructured":"Chen S, Bubeck D, MacDonald BT et al (2011) Structural and functional studies of LRP6 ectodomain reveal a platform for Wnt signaling. Dev Cell 21:848\u2013861. https:\/\/doi.org\/10.1016\/j.devcel.2011.09.007","journal-title":"Dev Cell"},{"key":"10395_CR44","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.phrs.2019.04.033","volume":"144","author":"C Ren","year":"2019","unstructured":"Ren C, Gu X, Li H et al (2019) The role of DKK1 in Alzheimer\u2019s disease: a potential intervention point of brain damage prevention? Pharmacol Res 144:331\u2013335. https:\/\/doi.org\/10.1016\/j.phrs.2019.04.033","journal-title":"Pharmacol Res"},{"key":"10395_CR45","doi-asserted-by":"publisher","first-page":"2309","DOI":"10.1074\/jbc.M406275200","volume":"280","author":"CA Gregory","year":"2005","unstructured":"Gregory CA, Perry AS, Reyes E et al (2005) Dkk-1-derived synthetic peptides and lithium chloride for the control and recovery of adult stem cells from bone marrow. J Biol Chem 280:2309\u20132323. https:\/\/doi.org\/10.1074\/jbc.M406275200","journal-title":"J Biol Chem"},{"key":"10395_CR46","doi-asserted-by":"publisher","first-page":"8461","DOI":"10.1021\/jm200996g","volume":"54","author":"V Palomo","year":"2011","unstructured":"Palomo V, Soteras I, Perez DI et al (2011) Exploring the binding sites of glycogen synthase kinase 3. identification and characterization of allosteric modulation cavities. J Med Chem 54:8461\u20138470. https:\/\/doi.org\/10.1021\/jm200996g","journal-title":"J Med Chem"},{"key":"10395_CR47","doi-asserted-by":"publisher","first-page":"571","DOI":"10.7150\/thno.14334","volume":"6","author":"MK Pandey","year":"2016","unstructured":"Pandey MK, DeGrado TR (2016) Glycogen synthase kinase-3 (GSK-3)-targeted therapy and imaging. Theranostics 6:571\u2013593. https:\/\/doi.org\/10.7150\/thno.14334","journal-title":"Theranostics"},{"key":"10395_CR48","doi-asserted-by":"publisher","first-page":"e0181542","DOI":"10.1371\/JOURNAL.PONE.0181542","volume":"12","author":"R Ochocka","year":"2017","unstructured":"Ochocka R, Hering A, Stefanowicz-Hajduk J et al (2017) The effect of mangiferin on skin: penetration, permeation and inhibition of ECM enzymes. PLoS ONE 12:e0181542. https:\/\/doi.org\/10.1371\/JOURNAL.PONE.0181542","journal-title":"PLoS ONE"},{"key":"10395_CR49","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.jtemb.2015.04.002","volume":"31","author":"P Kasbe","year":"2015","unstructured":"Kasbe P, Jangra A, Lahkar M (2015) Mangiferin ameliorates aluminium chloride-induced cognitive dysfunction via alleviation of hippocampal oxido-nitrosative stress, proinflammatory cytokines and acetylcholinesterase level. J Trace Elem Med Biol 31:107\u2013112. https:\/\/doi.org\/10.1016\/j.jtemb.2015.04.002","journal-title":"J Trace Elem Med Biol"},{"key":"10395_CR50","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.ejphar.2012.02.042","volume":"683","author":"SM Biradar","year":"2012","unstructured":"Biradar SM, Joshi H, Chheda TK (2012) Neuropharmacological effect of Mangiferin on brain cholinesterase and brain biogenic amines in the management of Alzheimer\u2019s disease. Eur J Pharmacol 683:140\u2013147. https:\/\/doi.org\/10.1016\/j.ejphar.2012.02.042","journal-title":"Eur J Pharmacol"}],"container-title":["Molecular Diversity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11030-022-10395-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11030-022-10395-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11030-022-10395-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T08:10:39Z","timestamp":1664871039000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11030-022-10395-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,11]]},"references-count":50,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10395"],"URL":"https:\/\/doi.org\/10.1007\/s11030-022-10395-8","relation":{},"ISSN":["1381-1991","1573-501X"],"issn-type":[{"value":"1381-1991","type":"print"},{"value":"1573-501X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,11]]},"assertion":[{"value":"17 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 January 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 February 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no potential conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All the authors have provided explicit consent for the publication of the article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}