Predes D , Maia LA , Matias I , Araujo HPM , Soares C , Barros-Aragão FGQ , Oliveira LFS , Reis RR , Amado NG , Simas ABC , Mendes FA , Gomes FCA , Figueiredo CP , Abreu JG .

                neurodegenerative disease

Xla Wt + wnt8a + Quercitrin (Fig. 2 defgh)

	Figure 1. Quercitrin potentiates the Wnt/β-catenin signaling pathway. (a) Reporter gene assay in RKO B/R cells treated with L-cell CM, Wnt3a CM or recombinant human Wnt3a. The cells were treated with the vehicle dimethyl sulfoxide (DMSO) or quercitrin for 24 h (n = 3, performed in triplicate, one-way ANOVA followed by Dunnett’s multiple comparisons test, * p < 0.05, ** p < 0.01, *** p < 0.001). Error bars denote mean ± SD. (b) TOPFLASH reporter gene assay in transfected HEK293T cells treated with L-cell CM or Wnt3a CM. The cells were treated with the vehicle DMSO or quercitrin for 24 h (n = 3, performed in triplicate, one-way ANOVA followed by Dunnett’s multiple comparisons test, * p < 0.05, *** p < 0.001). Error bars denote mean ± SD. (c) Reporter gene assay of RKO B/R cells treated for 6 h (n = 3, performed in triplicate, one-way ANOVA followed by Dunnett’s multiple comparisons test, *** p < 0.001). Error bars denote mean ± SD. (d) Reporter gene assay of RKO B/R cells treated for 12 h (n = 3, performed in triplicate, one-way ANOVA followed by Dunnett’s multiple comparisons test, *** p < 0.001). Error bars denote mean ± SD. (e) Immunoblot assay of RKO cells lysate after 4 h treatment. RKO cells were treated with L-cell CM (lane 1) or Wnt3a CM (lanes 2–4). (f) Densitometric analysis of (e) showing that quercitrin increases β-catenin protein levels (n = 4, one-way ANOVA followed by Dunnett’s multiple comparisons test, *** p < 0.001). Error bars denote mean ± SD. (g) Immunoblotting of RKO cells treated for 24 h. RKO cells were treated with L-cell CM (lane 1) or Wnt3a CM (lanes 2–4). (h) Densitometric analysis of (g) pLRP6/LRP6 protein levels revealing that quercitrin increases pLRP6 S1490 and decreases pβ-catenin S33/S37 protein levels (n = 4, performed in triplicate, one-way ANOVA followed by Dunnett’s multiple comparisons test, * p < 0.05, *** p < 0.001). Error bars denote mean ± SD. (i) Densitometric analysis of (g) pβ-catenin/β-catenin protein levels revealing that quercitrin decreases pβ-catenin S33/S37 protein levels (n = 4, one-way ANOVA followed by Dunnett’s multiple comparisons test, *** p < 0.001). Error bars denote mean ± SD.
	Figure 2. Quercitrin potentiates the Wnt/β-catenin signaling pathway in Xenopus laevis. (a–f) Representative embryos injected with increasing concentrations of xWnt8 mRNA into the ventral blastomere, co-injected with DMSO or 1.6 pmol quercitrin. The injection induces the formation of an incomplete (arrow head) or a complete secondary axis (arrow). (g) Phenotype quantification of (a–f). The coinjection with quercitrin increases the complete secondary axis phenotype occurrence. The number of embryos in each condition is shown above the graph bars. (h) S01234 reporter gene assay. Quercitrin coinjection potentiates the S01234 reporter gene activation induced by Xwnt8 mRNA (n = 2, performed in triplicate, Unpaired t-test comparing the DMSO and quercitrin injected groups. ** p < 0.01). Error bars represent mean ± SD. See Figure S2 for the injection scheme.
	Figure 3. Quercitrin facilitates GSK3 S9 phosphorylation and hinders GSK3 activity. (a–c) TOPFLASH reporter gene assay of HEK293T cells transfected with (a) β-catenin S33A, (b) β-catenin WT, or (c) LRP6 (n = 3, performed in triplicate, one-way ANOVA followed by Dunnett’s multiple comparisons test, ns = not significant). (d) Reporter gene assay of HEK293T cells treated with 0.3, 0.5, 0.7, and 1.0 μM of BIO, a GSK3 inhibitor. (n = 3, performed in triplicate, Two-way ANOVA followed by Bonferroni’s multiple comparisons test, * p < 0.05). Error bars denote mean ± SD. (e) GSK3 biosensor scheme. The biosensor contains the GFP protein at the N-terminus and a FLAG-tag at the C-terminus. The phosphorylation of the biosensor by GSK3 triggers its degradation. (f) Immunoblotting assay of HEK293T transfected with the GSK3 biosensor after 6 h treatment. Cells were treated with L-cell CM (lane 1) or Wnt3a CM (lanes 2–5). (g) Densitometric analysis of β-catenin/α-tubulin protein levels (n = 4, Unpaired t-test, two-tailed, *** p < 0.001). Error bars denote mean ± SD. (h) Densitometric analysis of GSK3 biosensor/α-tubulin protein levels showing that quercitrin treatment hinders GSK3 activity (n = 4, Unpaired t-test, two-tailed, *** p < 0.001). Error bars denote mean ± SD. (i) Immunoblotting of RKO cells lysate after 24 h treatment. RKO cells were treated with L-cell CM (lane 1) or Wnt3a CM (lanes 2–4). (j) Densitometry analysis of pGSK3βS9/GSK3β protein levels demonstrating that quercitrin increases the pGSK3βS9/GSK3β ratio (n = 4, one-way ANOVA followed by Dunnett’s multiple comparisons test, * p < 0.05). Error bars denote mean ± SD. (k) Reporter gene assay of RKO B/R cells treated with L-cell CM or Wnt3a CM, quercitrin, and 5 μM XAV939 for 24 h. The treatment reveals that XAV939 impairs the quercitrin potentiation effect (n = 3, performed in triplicate, one-way ANOVA followed by Dunnett’s multiple comparisons test considering Wnt3a CM + DMSO condition as control, * p < 0.05, *** p < 0.001, or considering Wnt3a CM + DMSO + XAV939 as the control condition, ‡‡‡ p < 0.001. An Unpaired t-test of DMSO and DMSO + XAV939 conditions was performed to assess the XAV939 effect on the reporter gene activity, †† p < 0.01). Error bars denote mean ± SD. (l) Scheme of quercitrin mechanism of action. Quercitrin hinders GSK3 activity, thus impairing β-catenin degradation and increasing its stabilization. The red arrow indicates β-catenin degradation. The black arrow denotes β-catenin translocation to the nucleus and Wnt target genes transcription.
	Figure 4. Quercitrin potentiates the canonical Wnt synaptogenic effect and rescues AβO-induced memory impairment in mice. (a–d) Synaptophysin and PSD-95 immunocytochemistry of E16 13DIV cultured hippocampal neurons treated with XAV939 and/or quercitrin for 24 h. Scale bars: 20 μm. (e) Synaptophysin/PSD-95 colocalized puncta quantification of (a–d), showing that quercitrin potentiates the recombinant Wnt-mediated synaptogenesis in vitro, which is impaired by XAV939 (n = 3, performed in duplicate, one-way ANOVA statistical analysis followed by Newman–Keuls multiple comparisons test. ** p < 0.01, comparing hWnt3a + DMSO, and hWnt3a + quercitrin conditions. †† p < 0.01, comparing hWnt3a + quercitrin and hWnt3a + quercitrin + XAV939 conditions). Scale bars denote 20 μm. (f) Immunoblotting analysis of injected mice hippocampus lysate staining for β-catenin, synaptophysin, and PSD-95. β-actin was used as a cytoskeleton loading control. GAPDH was used as a metabolic loading control. Each lane represents a different animal. The animals were injected with vehicle (lanes 1–4), vehicle + AβO (lanes 5–8), or quercitrin + AβO (lanes 9–12). (g–l) Densitometric quantification of (f) showing that quercitrin rescues the decreased β-catenin, synaptophysin, and PSD-95 protein levels caused by AβO ICV injection (n = 4, Unpaired t-test, two-tailed, considering the AβO + vehicle as the control condition, * p < 0.05, ** p < 0.01, *** p < 0.001). Error bars denote mean ± SEM. Each white circle denotes one animal. (m) Workflow scheme of the i.c.v. injections, object recognition training, and testing. Red square represents a familiar object, and blue object represents a novel object. (n) Novel object recognition (NOR) test, 24 h after i.c.v. injection. Quercitrin reverses the memory impairment caused by AβO injection, which is impaired by XAV939 (n = 10, One sample t-test, theoretical mean value of 50%, * p < 0.05, ** p < 0.01). F: familiar object, N: novel object. Error bar represents mean ± SEM. See also Figure S5 for NOR training and open field arena test data.
	Figure S1. Quercitrin potentiates the signaling after Wnt ligand stimulation. TOPFLASH assay of HEK293T transfected with increasing amounts (1, 10, 30 ng/well) of hWnt3a plasmid. HEK293T cells were treated overnight with quercitrin or quercetin (a Wnt signaling inhibitor). (n=3, performed in triplicate, two-way ANOVA analysis considering the DMSO as the control condition followed by a Dunnett multiple comparison test. *p<0.05, **p<0.01). Error bars represent mean ± SD
	Figure S2. Injection scheme of 4-cell Xenopus laevis embryos. (a) For the Axis Duplication Assay, the ventral blastomeres were equatorially injected. (b) For the S01234 reporter gene assay, we injected one ventral and one dorsal blastomeres.
	Figure S3. Quercitrin does not potentiate the Wnt signaling in the SW480 tumoral cell line. (a) RKO B/R cell line was treated with L-cell CM, Wnt3a CM, the vehicle DMSO, or increasing concentrations of quercitrin (n=3, performed in triplicate, one-way ANOVA followed by Dunnett's multiple comparisons test, **p < 0.01, ***p < 0.001). Error bars denote mean ± SD. (b) SW480 B/R reporter gene cell lines were treated with DMSO or increasing concentrations of quercitrin (n=3, performed in triplicate, one-way ANOVA followed by Dunnett's multiple comparisons test, *p < 0.05, **p < 0.01). Error bars denote mean ± SD.
	Figure S4. Quercitrin per se does not induce synaptogenesis in vitro. (a) Protocol illustration of in vitro hippocampus neuronal culture and treatment. (b-c) Synaptophysin and PSD-95 immunostaining of hippocampal neuronal culture. (d) Colocalized puncta quantification shows that 10 μM quercitrin per se does not induce synaptogenesis (n=3, performed in duplicate, Welch t-test statistical analysis). Error bars denote mean ± SEM. Scale bars denote 10 μm
	Figure S5. ICV injection does not alter the experimental exploration time of injected mice. (a) Total exploration time (s) of the left and right objects in the novel object recognition (NOR) training. (b) Exploration time (% of total time) in both objects under training and testing conditions. (c) Distance travelled (m) in the Open Field analysis. (d) Time (s) in center during the Open Field analysis.

Alvarez, Wnt-3a overcomes beta-amyloid toxicity in rat hippocampal neurons. 2004, Pubmed

Alvarez, Wnt-3a overcomes beta-amyloid toxicity in rat hippocampal neurons. 2004, Pubmed
Amado, Isoquercitrin suppresses colon cancer cell growth in vitro by targeting the Wnt/β-catenin signaling pathway. 2014, Pubmed , Xenbase
Amado, Flavonoids and Wnt/β-catenin signaling: potential role in colorectal cancer therapies. 2014, Pubmed
Amado, Effects of natural compounds on Xenopus embryogenesis: a potential read out for functional drug discovery targeting Wnt/β-catenin signaling. 2012, Pubmed , Xenbase
Amado, Isoquercitrin isolated from Hyptis fasciculata reduces glioblastoma cell proliferation and changes beta-catenin cellular localization. 2009, Pubmed
Amaral, Telocinobufagin and Marinobufagin Produce Different Effects in LLC-PK1 Cells: A Case of Functional Selectivity of Bufadienolides. 2018, Pubmed
Anastas, WNT signalling pathways as therapeutic targets in cancer. 2013, Pubmed
Ayaz, Flavonoids as Prospective Neuroprotectants and Their Therapeutic Propensity in Aging Associated Neurological Disorders. 2019, Pubmed
Baron, WNT signaling in bone homeostasis and disease: from human mutations to treatments. 2013, Pubmed
Bensalem, Polyphenol-rich extract from grape and blueberry attenuates cognitive decline and improves neuronal function in aged mice. 2018, Pubmed
Bossy-Wetzel, Molecular pathways to neurodegeneration. 2004, Pubmed
Brannon, A beta-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus. 1997, Pubmed , Xenbase
Breen, Poorly differentiated colon carcinoma cell lines deficient in alpha-catenin expression express high levels of surface E-cadherin but lack Ca(2+)-dependent cell-cell adhesion. 1993, Pubmed
Brickman, Enhancing dentate gyrus function with dietary flavanols improves cognition in older adults. 2014, Pubmed
Cha, Hovenia dulcis Thunb extract and its ingredient methyl vanillate activate Wnt/β-catenin pathway and increase bone mass in growing or ovariectomized mice. 2014, Pubmed
Chen, Chemistry, pharmacokinetics, pharmacological activities, and toxicity of Quercitrin. 2022, Pubmed
Chen, Activity-dependent synaptic Wnt release regulates hippocampal long term potentiation. 2006, Pubmed
Chiquet, Variation in WNT genes is associated with non-syndromic cleft lip with or without cleft palate. 2008, Pubmed
Comalada, In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-kappaB pathway. 2005, Pubmed
Córdoba, Quercitrin Nanocoated Implant Surfaces Reduce Osteoclast Activity In Vitro and In Vivo. 2018, Pubmed
Currais, Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer's disease transgenic mice. 2014, Pubmed
de Almeida, Piperine suppresses the Wnt/β-catenin pathway and has anti-cancer effects on colorectal cancer cells. 2020, Pubmed
de Andrade Teles, Flavonoids as Therapeutic Agents in Alzheimer's and Parkinson's Diseases: A Systematic Review of Preclinical Evidences. 2018, Pubmed
De Ferrari, Activation of Wnt signaling rescues neurodegeneration and behavioral impairments induced by beta-amyloid fibrils. 2003, Pubmed
de Sampaio e Spohr, Effects of the flavonoid casticin from Brazilian Croton betulaster in cerebral cortical progenitors in vitro: direct and indirect action through astrocytes. 2010, Pubmed
Devore, Dietary intakes of berries and flavonoids in relation to cognitive decline. 2012, Pubmed
Dias, A historical overview of natural products in drug discovery. 2012, Pubmed
Dickins, Wnts in action: from synapse formation to synaptic maintenance. 2013, Pubmed
Diniz, Astrocyte-induced synaptogenesis is mediated by transforming growth factor β signaling through modulation of D-serine levels in cerebral cortex neurons. 2012, Pubmed
Dohare, Glycogen synthase kinase-3β inhibition enhances myelination in preterm newborns with intraventricular hemorrhage, but not recombinant Wnt3A. 2018, Pubmed
Fonseca, Derricin and derricidin inhibit Wnt/β-catenin signaling and suppress colon cancer cell growth in vitro. 2015, Pubmed , Xenbase
Frame, A common phosphate binding site explains the unique substrate specificity of GSK3 and its inactivation by phosphorylation. 2001, Pubmed
Gadotti, Antinociceptive action of the extract and the flavonoid quercitrin isolated from Bauhinia microstachya leaves. 2005, Pubmed
Gálvez, Effect of quercitrin on lactose-induced chronic diarrhoea in rats. 1995, Pubmed
Gálvez, Antidiarrhoeic activity of quercitrin in mice and rats. 1993, Pubmed
Gammons, Wnt Signalosome Assembly by DEP Domain Swapping of Dishevelled. 2016, Pubmed
Garner, Wnt is here! Could Wnt signalling be promoted to protect against Alzheimer disease?: An Editorial for 'Wnt signaling loss accelerates the appearance of neuropathological hallmarks of Alzheimer's disease in J20- APP transgenic and wild-type mice' on doi:10.1111/jnc.14278. 2018, Pubmed
Giannini, Analysis of beta-catenin aggregation and localization using GFP fusion proteins: nuclear import of alpha-catenin by the beta-catenin/Tcf complex. 2000, Pubmed
Glass, Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. 2005, Pubmed
Guo, Wnt/β-catenin signaling pathway activates melanocyte stem cells in vitro and in vivo. 2016, Pubmed
Hardy, Alzheimer's disease: the amyloid cascade hypothesis. 1992, Pubmed
He, Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo. 2018, Pubmed
Hernández, Spatial learning deficit in transgenic mice that conditionally over-express GSK-3beta in the brain but do not form tau filaments. 2002, Pubmed
Hooper, The GSK3 hypothesis of Alzheimer's disease. 2008, Pubmed
Huang, Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. 2009, Pubmed
Inestrosa, Emerging roles of Wnts in the adult nervous system. 2010, Pubmed
Jang, Secreted frizzled-related protein 3 regulates activity-dependent adult hippocampal neurogenesis. 2013, Pubmed
Kahn, Can we safely target the WNT pathway? 2014, Pubmed
Kennell, Wnt signaling inhibits adipogenesis through beta-catenin-dependent and -independent mechanisms. 2005, Pubmed
Kim, Flavonoids from Acer okamotoanum Inhibit Adipocyte Differentiation and Promote Lipolysis in the 3T3-L1 Cells. 2020, Pubmed
Kim, Wnt stabilization of β-catenin reveals principles for morphogen receptor-scaffold assemblies. 2013, Pubmed , Xenbase
Kneidinger, Activation of the WNT/β-catenin pathway attenuates experimental emphysema. 2011, Pubmed
Korinek, Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. 1997, Pubmed
Kusserow, Unexpected complexity of the Wnt gene family in a sea anemone. 2005, Pubmed
Lee, Wnt3a upregulates brain-derived insulin by increasing NeuroD1 via Wnt/β-catenin signaling in the hypothalamus. 2016, Pubmed
Lie, Wnt signalling regulates adult hippocampal neurogenesis. 2005, Pubmed
Lu, Wnt Drug Discovery: Weaving Through the Screens, Patents and Clinical Trials. 2016, Pubmed
Lucas, Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. 2001, Pubmed
MacDonald, Wnt/beta-catenin signaling: components, mechanisms, and diseases. 2009, Pubmed , Xenbase
MacDonald, Wnt signal amplification via activity, cooperativity, and regulation of multiple intracellular PPPSP motifs in the Wnt co-receptor LRP6. 2008, Pubmed , Xenbase
Magdesian, Amyloid-beta binds to the extracellular cysteine-rich domain of Frizzled and inhibits Wnt/beta-catenin signaling. 2008, Pubmed
Maher, The Potential of Flavonoids for the Treatment of Neurodegenerative Diseases. 2019, Pubmed
Maia, Advances in the use of Xenopus for successful drug screening. 2017, Pubmed , Xenbase
Major, Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling. 2007, Pubmed , Xenbase
Martinez, Canonical Wnt Signaling Modulates the Expression of Pre- and Postsynaptic Components in Different Temporal Patterns. 2020, Pubmed
Matias, Functions of flavonoids in the central nervous system: Astrocytes as targets for natural compounds. 2016, Pubmed
Matias, Flavonoid Hesperidin Induces Synapse Formation and Improves Memory Performance through the Astrocytic TGF-β1. 2017, Pubmed
McLeod, Wnt proteins as modulators of synaptic plasticity. 2018, Pubmed
Meijer, GSK-3-selective inhibitors derived from Tyrian purple indirubins. 2003, Pubmed , Xenbase
Metcalfe, Inhibition of GSK3 by Wnt signalling--two contrasting models. 2011, Pubmed
Munemitsu, Deletion of an amino-terminal sequence beta-catenin in vivo and promotes hyperphosporylation of the adenomatous polyposis coli tumor suppressor protein. 1996, Pubmed
Muzitano, Quercitrin: an antileishmanial flavonoid glycoside from Kalanchoe pinnata. 2006, Pubmed
Näslund, Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline. NULL, Pubmed
Ng, Plant alkaloids as drug leads for Alzheimer's disease. 2015, Pubmed
Niehrs, The complex world of WNT receptor signalling. 2012, Pubmed
Nones, Effects of the flavonoid hesperidin in cerebral cortical progenitors in vitro: indirect action through astrocytes. 2012, Pubmed
Nones, The flavonoids hesperidin and rutin promote neural crest cell survival. 2012, Pubmed
Nusse, Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. 2017, Pubmed
Okamoto, Reduction in paracrine Wnt3 factors during aging causes impaired adult neurogenesis. 2011, Pubmed
Oliveira, Therapeutic Potential of Naturally Occurring Small Molecules to Target the Wnt/β-Catenin Signaling Pathway in Colorectal Cancer. 2022, Pubmed
Park, Quercetin, a potent inhibitor against beta-catenin/Tcf signaling in SW480 colon cancer cells. 2005, Pubmed
Park, WNTs in synapse formation and neuronal circuitry. 2012, Pubmed
Park, Novel small molecule activators of beta-catenin-mediated signaling pathway: structure-activity relationships of indirubins. 2009, Pubmed
Parr, Activation of the Wnt/β-catenin pathway represses the transcription of the β-amyloid precursor protein cleaving enzyme (BACE1) via binding of T-cell factor-4 to BACE1 promoter. 2015, Pubmed
Pei, Distribution of active glycogen synthase kinase 3beta (GSK-3beta) in brains staged for Alzheimer disease neurofibrillary changes. 1999, Pubmed
Peterson-Nedry, Unexpectedly robust assembly of the Axin destruction complex regulates Wnt/Wg signaling in Drosophila as revealed by analysis in vivo. 2008, Pubmed
Predes, The Chalcone Lonchocarpin Inhibits Wnt/β-Catenin Signaling and Suppresses Colorectal Cancer Proliferation. 2019, Pubmed , Xenbase
Rivera, Andrographolide recovers cognitive impairment in a natural model of Alzheimer's disease (Octodon degus). 2016, Pubmed
Rosso, WNT signaling in neuronal maturation and synaptogenesis. 2013, Pubmed
Satué, Quercitrin and taxifolin stimulate osteoblast differentiation in MC3T3-E1 cells and inhibit osteoclastogenesis in RAW 264.7 cells. 2013, Pubmed
Seib, Loss of Dickkopf-1 restores neurogenesis in old age and counteracts cognitive decline. 2013, Pubmed
Selkoe, The amyloid hypothesis of Alzheimer's disease at 25 years. 2016, Pubmed
Shi, Wnt and Notch signaling pathway involved in wound healing by targeting c-Myc and Hes1 separately. 2015, Pubmed
Shruster, Wnt signaling pathway overcomes the disruption of neuronal differentiation of neural progenitor cells induced by oligomeric amyloid β-peptide. 2011, Pubmed
Sies, Polyphenols and health: update and perspectives. 2010, Pubmed
Song, Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion. 2009, Pubmed
Stamos, Structural basis of GSK-3 inhibition by N-terminal phosphorylation and by the Wnt receptor LRP6. 2014, Pubmed
Taelman, Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes. 2010, Pubmed , Xenbase
Tapia-Rojas, Andrographolide activates the canonical Wnt signalling pathway by a mechanism that implicates the non-ATP competitive inhibition of GSK-3β: autoregulation of GSK-3β in vivo. 2015, Pubmed
Tapia-Rojas, Loss of canonical Wnt signaling is involved in the pathogenesis of Alzheimer's disease. 2018, Pubmed
Tapia-Rojas, Wnt signaling loss accelerates the appearance of neuropathological hallmarks of Alzheimer's disease in J20-APP transgenic and wild-type mice. 2018, Pubmed
Toledo, Activation of Wnt signaling by lithium and rosiglitazone reduced spatial memory impairment and neurodegeneration in brains of an APPswe/PSEN1DeltaE9 mouse model of Alzheimer's disease. 2010, Pubmed
Tosti, Topical application of the Wnt/β-catenin activator methyl vanillate increases hair count and hair mass index in women with androgenetic alopecia. 2016, Pubmed
Townsend, Effects of secreted oligomers of amyloid beta-protein on hippocampal synaptic plasticity: a potent role for trimers. 2006, Pubmed
Unno, Green Tea Catechins Trigger Immediate-Early Genes in the Hippocampus and Prevent Cognitive Decline and Lifespan Shortening. 2020, Pubmed
Vargas, In vivo activation of Wnt signaling pathway enhances cognitive function of adult mice and reverses cognitive deficits in an Alzheimer's disease model. 2014, Pubmed
Vargas, WASP-1, a canonical Wnt signaling potentiator, rescues hippocampal synaptic impairments induced by Aβ oligomers. 2015, Pubmed
Wang, GSK-3β as a target for protection against transient cerebral ischemia. 2017, Pubmed
Yang, Fisetin improves lead-induced neuroinflammation, apoptosis and synaptic dysfunction in mice associated with the AMPK/SIRT1 and autophagy pathway. 2019, Pubmed
Zhang, 7,8-dihydroxyflavone prevents synaptic loss and memory deficits in a mouse model of Alzheimer's disease. 2014, Pubmed
Zhang, Small-molecule synergist of the Wnt/beta-catenin signaling pathway. 2007, Pubmed , Xenbase
Zhang, Destabilization of beta-catenin by mutations in presenilin-1 potentiates neuronal apoptosis. 1998, Pubmed