Wnt signaling pathway dysregulation in the aging brain: lessons from the Octodon degus

Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities

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Frequency of Stages of Alzheimer-Related Lesions in Different Age Categories

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Function and biological roles of the Dickkopf family of Wnt modulators

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Wnt signaling in development and tissue homeostasis

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Secreted and transmembrane wnt inhibitors and activators

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Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer’s Disease Progression

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Emerging roles of Wnts in the adult nervous system

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Destabilization of β-catenin by mutations in presenilin-1 potentiates neuronal apoptosis

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Three decades of Wnts: a personal perspective on how a scientific field developed

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Induction of Dickkopf-1, a Negative Modulator of the Wnt Pathway, Is Associated with Neuronal Degeneration in Alzheimer's Brain

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Interaction of Frizzled Related Protein (FRP) with Wnt Ligands and the Frizzled Receptor Suggests Alternative Mechanisms for FRP Inhibition of Wnt Signaling

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Apolipoprotein E Affects the Rate of Alzheimer Disease Expression: β-Amyloid Burden Is a Secondary Consequence Dependent on APOE Genotype and Duration of Disease

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Loss of Dickkopf-1 Restores Neurogenesis in Old Age and Counteracts Cognitive Decline

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Activation of Wnt signaling by lithium and rosiglitazone reduced spatial memory impairment and neurodegeneration in brains of an APPswe/PSEN1ΔE9 mouse model of Alzheimer's disease

Toledo, E. M., & Inestrosa, N. C. (2009) · Molecular Psychiatry · doi:10.1038/mp.2009.72 · Cited by 290 · see citing works

Common genetic variation within the Low-Density Lipoprotein Receptor-Related Protein 6 and late-onset Alzheimer's disease

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Wnt signaling deregulation in the aging and Alzheimer’s brain

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Deficiency in LRP6-mediated Wnt signaling contributes to synaptic abnormalities and amyloid pathology in Alzheimer’s disease

Liu, C.-C., Tsai, C.-W., Deak, F., Rogers, J., Penuliar, M., Sung, Y. M., Maher, J. N., Fu, Y., Li, X., Xu, H., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.08.048 · Cited by 222 · see citing works

Wnt-7a Modulates the Synaptic Vesicle Cycle and Synaptic Transmission in Hippocampal Neurons*

Cerpa, W., Godoy, J., Alfaro, I. E., Farías, G., Metcalfe, M., Fuentealba, R., Bonansco, C., & Inestrosa, N. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m705943200 · Cited by 216 · see citing works

The role of Wnt signaling in neuronal dysfunction in Alzheimer's Disease

Inestrosa, N. C., & Toledo, E. M. (2008) · Molecular Neurodegeneration · doi:10.1186/1750-1326-3-9 · Cited by 206 · see citing works

Structural Basis of Wnt Signaling Inhibition by Dickkopf Binding to LRP5/6

Ahn, V. E., Chu, M. L.-H., Choi, H., Tran, D. P., Abo, A., & Weis, W. I. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.09.003 · Cited by 202 · see citing works

Wnt-5a/JNK Signaling Promotes the Clustering of PSD-95 in Hippocampal Neurons

Farı́as, G. G., Alfaro, I. E., Cerpa, W. F., Grabowski, C. P., Godoy, J. A., Bonansco, C., & Inestrosa, N. C. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808986200 · Cited by 200 · see citing works

Multiprotein complexes governing Wnt signal transduction

Gammons, M. V. R., & Bienz, M. (2017) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2017.10.008 · Cited by 199 · see citing works

The secreted Wnt antagonist Dickkopf-1 is required for amyloid β-mediated synaptic loss

Purro, S. A., Dickins, E. M., & Salinas, P. C. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.4562-11.2012 · Cited by 195 · see citing works

Wnt signalling in neuronal differentiation and development

Inestrosa, N. C., & Varela‐Nallar, L. (2014) · Cell and Tissue Research · doi:10.1007/s00441-014-1996-4 · Cited by 162 · see citing works

GSK3 and Alzheimer’s disease: facts and fiction…

Kremer, A. (2011) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2011.00017 · Cited by 155 · see citing works

GSK‐3: A key player in neurodegeneration and memory

Giese, K.-P. (2009) · IUBMB Life · doi:10.1002/iub.187 · Cited by 150 · see citing works

In vivoActivation ofWntSignaling Pathway Enhances Cognitive Function of Adult Mice and Reverses Cognitive Deficits in an Alzheimer's Disease Model

Vargas, J., Fuenzalida, M., & Inestrosa, N. C. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0862-13.2014 · Cited by 147 · see citing works

Functional Characterization of WNT7A Signaling in PC12 Cells

Caricasole, A., Ferraro, T., Iacovelli, L., Barletta, E., Caruso, A., Melchiorri, D., Terstappen, G. C., & Nicoletti, F. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300191200 · Cited by 142 · see citing works

Characterization of the Wnt Inhibitors Secreted Frizzled-Related Proteins (SFRPs) in Human Adipose Tissue

Ehrlund, A., Mejhert, N., Lorente‐Cebrián, S., Åström, G., Dahlman, I. A., Laurencikiene, J., & Rydén, M. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-3416 · Cited by 140 · see citing works

A review for the neuroprotective effects of andrographolide in the central nervous system

Lu, J., Ma, Y., Wu, J., Huang, H., Wang, X., Chen, Z., Chen, J., He, H., & Huang, C. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109078 · Cited by 134 · see citing works

Inhibition of Wnt signaling, modulation of Tau phosphorylation and induction of neuronal cell death by DKK1

Scali, C., Caraci, F., Gianfriddo, M., Diodato, E., Roncarati, R., Pollio, G., Gaviraghi, G., Copani, A., Nicoletti, F., Terstappen, G. C., et al. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.06.016 · Cited by 128 · see citing works

Human-like rodent amyloid-β-peptide determines Alzheimer pathology in aged wild-type Octodon degu

Inestrosa, N. C., Reyes, A. E., Chacón, M. A., Cerpa, W. F., Villalón, A., Montiel, J. F., Merabachvili, G., Aldunate, R., Bozinovic, F., & Aboitiz, F. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.09.016 · Cited by 124 · see citing works

Impaired Wnt Signaling in the Prefrontal Cortex of Alzheimer’s Disease

Folke, J., Pakkenberg, B., & Brudek, T. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1103-z · Cited by 123 · see citing works

Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice

Serrano, F. G., Tapia‐Rojas, C., Carvajal, F. J., Hancke, J. L., Cerpa, W. F., & Inestrosa, N. C. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-61 · Cited by 117 · see citing works

Wnt-7a Induces Presynaptic Colocalization of α7-Nicotinic Acetylcholine Receptors and Adenomatous Polyposis Coli in Hippocampal Neurons

Farías, G. G., Vallés, A. S., Colombres, M., Godoy, J. A., Toledo, E. M., Lukas, R. J., Barrantes, F. J., & Inestrosa, N. C. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3934-06.2007 · Cited by 108 · see citing works

Octodon degus: A Diurnal, Social, and Long-lived Rodent

Lee, T. M. (2004) · ILAR Journal · doi:10.1093/ilar.45.1.14 · Cited by 105 · see citing works

Wnt Signaling in the Central Nervous System: New Insights in Health and Disease

Oliva, C. A., Montecinos-Oliva, C., & Inestrosa, N. C. (2018) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2017.11.018 · Cited by 97 · see citing works

Wnt Antagonist SFRP1 Functions as a Secreted Mediator of Senescence

Elzi, D. J., Song, M., Hakala, K. W., Weintraub, S. T., & Shiio, Y. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.06023-11 · Cited by 88 · see citing works

Wnt signaling loss accelerates the appearance of neuropathological hallmarks of Alzheimer's disease in J20‐ APP transgenic and wild‐type mice

Tapia‐Rojas, C., & Inestrosa, N. C. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14278 · Cited by 87 · see citing works

Andrographolide recovers cognitive impairment in a natural model of Alzheimer's disease (Octodon degus)

Rivera, D. S., Lindsay, C. B., Codocedo, J. F., Morel-Letelier, I., Pinto, C., Cisternas, P., Bozinovic, F., & Inestrosa, N. C. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.06.021 · Cited by 86 · see citing works

Andrographolide activates the canonical Wnt signalling pathway by a mechanism that implicates the non-ATP competitive inhibition of GSK-3β: autoregulation of GSK-3βin vivo

Tapia‐Rojas, C., Schüller, A., Lindsay, C. B., Ureta, R. C., Mejías-Reyes, C., Hancke, J. L., Melo, F., & Inestrosa, N. C. (2014) · Biochemical Journal · doi:10.1042/bj20140207 · Cited by 84 · see citing works

Elevated levels of Secreted-Frizzled-Related-Protein 1 contribute to Alzheimer’s disease pathogenesis

Esteve, P., Rueda‐Carrasco, J., Mateo, M. I., Martín‐Bermejo, M. J., Draffin, J. E., Pereyra, G., Sandonís, Á., Crespo, I., Moreno, I., Aso, E., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0432-1 · Cited by 78 · see citing works

Inhibition of Wnt signaling induces amyloidogenic processing of amyloid precursor protein and the production and aggregation of Amyloid‐β (Aβ)42 peptides

Tapia‐Rojas, C., Burgos, P. V., & Inestrosa, N. C. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13873 · Cited by 76 · see citing works

Andrographolide Activates Keap1/Nrf2/ARE/HO-1 Pathway in HT22 Cells and Suppresses Microglial Activation by Aβ42through Nrf2-Related Inflammatory Response

Seo, J. Y., Pyo, E., An, J., Kim, J., Sung, S. H., & Oh, W. K. (2017) · Mediators of Inflammation · doi:10.1155/2017/5906189 · Cited by 70 · see citing works

The emerging role of Wnt signaling dysregulation in the understanding and modification of age-associated diseases

García‐Velázquez, L., & Arias, C. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.06.001 · Cited by 70 · see citing works

A network-based analysis of key pharmacological pathways of Andrographis paniculata acting on Alzheimer's disease and experimental validation

Gu, L., Lü, J., Li, Q., Wu, N., Zhang, L., Li, H., Xing, W., & Zhang, X. (2019) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2019.112488 · Cited by 67 · see citing works

Age-related brain pathology in Octodon degu: Blood vessel, white matter and Alzheimer-like pathology

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Phospho-β-Catenin Accumulation in Alzheimer's Disease and in Aggresomes Attributable to Proteasome Dysfunction

Ghanevati, M., & Miller, C. A. (2005) · Journal of Molecular Neuroscience · doi:10.1385/jmn:25:1:079 · Cited by 64 · see citing works

Andrographolide Stimulates Neurogenesis in the Adult Hippocampus

Varela‐Nallar, L., Arredondo, S. B., Tapia‐Rojas, C., Hancke, J. L., & Inestrosa, N. C. (2015) · Neural Plasticity · doi:10.1155/2015/935403 · Cited by 61 · see citing works

Role of Wnt Signaling in Tissue Fibrosis, Lessons from Skeletal Muscle and Kidney

Cisternas, P., Vio, C. P., & Inestrosa, N. C. (2014) · Current Molecular Medicine · doi:10.2174/1566524014666140414210346 · Cited by 55 · see citing works

Andrographolide Protects PC12 Cells Against β-Amyloid-Induced Autophagy-Associated Cell Death Through Activation of the Nrf2-Mediated p62 Signaling Pathway

Gu, L., Yu, Q., Li, Q., Zhang, L., Lü, H., & Zhang, X. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19092844 · Cited by 54 · see citing works

Alzheimer’s Disease-Related Protein Expression in the Retina of Octodon degus

Du, L. Y., Chang, L., Ardiles, Á. O., Tapia‐Rojas, C., Araya, J., Inestrosa, N. C., Palacios, A. G., & Acosta, M. L. (2015) · PLoS ONE · doi:10.1371/journal.pone.0135499 · Cited by 47 · see citing works

Andrographolide Reduces Neuroinflammation and Oxidative Stress in Aged Octodon degus

Lindsay, C. B., Zolezzi, J. M., Rivera, D. S., Cisternas, P., Bozinovic, F., & Inestrosa, N. C. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-01784-6 · Cited by 47 · see citing works

Age Progression of Neuropathological Markers in the Brain of the Chilean Rodent Octodon degus, a Natural Model of A lzheimer's Disease

Inestrosa, N. C., Ríos, J. A., Cisternas, P., Tapia‐Rojas, C., Rivera, D. S., Braidy, N., Zolezzi, J. M., Godoy, J. A., Carvajal, F. J., Ardiles, Á. O., et al. (2014) · Brain Pathology · doi:10.1111/bpa.12226 · Cited by 44 · see citing works

Wnt-7a Stimulates Dendritic Spine Morphogenesis and PSD-95 Expression Through Canonical Signaling

Ramos‐Fernández, E., Tapia‐Rojas, C., Ramírez, V. T., & Inestrosa, N. C. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1162-1 · Cited by 37 · see citing works

Multi-Target β-Protease Inhibitors from Andrographis paniculata: In Silico and In Vitro Studies

Panche, A. N., Chandra, S., & Diwan, A. (2019) · Plants · doi:10.3390/plants8070231 · Cited by 30 · see citing works

Synthesis of andrographolide analogues and their neuroprotection and neurite outgrowth-promoting activities

Xu, Y., Wei, H., Wang, J., Wang, W., & Gao, J. (2019) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2019.04.025 · Cited by 29 · see citing works

New Insights into the Spontaneous Human Alzheimer’s Disease-Like Model Octodon degus : Unraveling Amyloid-β Peptide Aggregation and Age-Related Amyloid Pathology

Cisternas, P., Zolezzi, J. M., Lindsay, C. B., Rivera, D. S., Martinez, A. N., Bozinovic, F., & Inestrosa, N. C. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180729 · Cited by 26 · see citing works

Wnt signaling pathway improves central inhibitory synaptic transmission in a mouse model of Duchenne muscular dystrophy

Fuenzalida, M., Espinoza, C., Pérez, M. Á., Tapia‐Rojas, C., Cuitiño, L., Brandan, E., & Inestrosa, N. C. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.11.018 · Cited by 24 · see citing works

Influence of the rs1080985 Single Nucleotide Polymorphism of the CYP2D6 Gene and APOE Polymorphism on the Response to Donepezil Treatment in Patients with Alzheimer's Disease in China

Liu, M., Zhang, Y., Huo, Y. R., Liu, S., Liu, S., Wang, J., Wang, C., Wang, J., & Ji, Y. (2014) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000367596 · Cited by 18 · see citing works

Age-related increase in Wnt inhibitor causes a senescence-like phenotype in human cardiac stem cells

Nakamura, T., Hosoyama, T., Murakami, J., Samura, M., Ueno, K., Kurazumi, H., Suzuki, R., Mikamo, A., & Hamano, K. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.04.110 · Cited by 16 · see citing works

Diterpenes and the crosstalk with the arachidonic acid pathways, relevance in neurodegeneration

Inestrosa, N., & Zolezzi, J. M. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.257521 · Cited by 1 · see citing works

Primary cilia and ciliary signaling pathways in aging and age-related brain disorders

Ma, R., Kutchy, N. A., Chen, L., Meigs, D. D., & Hu, G. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105607 · Cited by 114 · see citing works

Molecular mechanisms of developmental pathways in neurological disorders: a pharmacological and therapeutic review

Jha, N. K., Chen, W., Kumar, S., Dubey, R., Tsai, L.-W., Kar, R., Jha, S. K., Gupta, P. K., Sharma, A., Gundamaraju, R., et al. (2022) · Open Biology · doi:10.1098/rsob.210289 · Cited by 59 · see citing works

Alzheimer’s Disease, Neural Plasticity, and Functional Recovery

Mercerón‐Martínez, D., Ibaceta-González, C., Salazar, C., Almaguer‐Melian, W., Bergado, J. A., & Palacios, A. G. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201178 · Cited by 48 · see citing works

The involvement of the Wnt/β-catenin signaling cascade in fibrosis progression and its therapeutic targeting by relaxin

Somanader, D. V. N., Zhao, P., Widdop, R. E., & Samuel, C. S. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116130 · Cited by 46 · see citing works

Unlocking Hope: Therapeutic Advances and Approaches in Modulating the Wnt Pathway for Neurodegenerative Diseases

Faraji, N., Ebadpour, N., Abavisani, M., & Gorji, A. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04462-4 · Cited by 37 · see citing works

Spatially resolved transcriptome of the aging mouse brain

Wu, C., Tu, T., Xie, M., Wang, Y., Yan, B., Gong, Y., Zhang, J., Zhou, X., & Xie, Z. (2024) · Aging Cell · doi:10.1111/acel.14109 · Cited by 32 · see citing works

WNT Signaling Is a Key Player in Alzheimer’s Disease

Inestrosa, N. C., Tapia‐Rojas, C., Cerpa, W. F., Cisternas, P., & Zolezzi, J. M. (2021) · Handbook of experimental pharmacology · doi:10.1007/164_2021_532 · Cited by 28 · see citing works

APOE3 Christchurch modulates β-catenin/Wnt signaling in iPS cell-derived cerebral organoids from Alzheimer’s cases

Perez-Corredor, P., Vanderleest, T. E., Vacano, G. N., Sanchez, J. S., Villalba-Moreno, N. D., Marino, C., Krasemann, S., Mendivil-Perez, M. A., Aguillón, D., Jiménez-Del-Río, M., et al. (2024) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2024.1373568 · Cited by 28 · see citing works

Molecular Insights to the Wnt Signaling During Alzheimer’s Disorder: a Potential Target for Therapeutic Interventions

Nagu, P., Sharma, V., Behl, T., Pathan, A. K., & Mehta, V. (2022) · Journal of Molecular Neuroscience · doi:10.1007/s12031-021-01940-5 · Cited by 28 · see citing works

Neurobiological Promises of the Bitter Diterpene Lactone Andrographolide

Hossain, R., Quispe, C., Herrera‐Bravo, J., Beltrán, J. F., Islam, M. T., Shaheen, S., Martins, N. A., Martorell, M., Kumar, M., Sharifi‐Rad, J., et al. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/3079577 · Cited by 27 · see citing works

The transcriptional landscape of Alzheimer’s disease and its association with Wnt signaling pathway

Martínez, M., & Inestrosa, N. C. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.06.029 · Cited by 25 · see citing works

Wnt Signaling in the Adult Hippocampal Neurogenic Niche

Arredondo, S. B., Valenzuela-Bezanilla, D., Santibanez, S. H., & Varela‐Nallar, L. (2022) · Stem Cells · doi:10.1093/stmcls/sxac027 · Cited by 21 · see citing works

Menopause and development of Alzheimer’s disease: Roles of neural glucose metabolism and Wnt signaling

Villaseca, P., Cisternas, P., & Inestrosa, N. C. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1021796 · Cited by 21 · see citing works

Octodon degus: a natural model of multimorbidity for ageing research

Cuenca‐Bermejo, L., Pizzichini, E., Cuello, A. M. G., Stefano, M. E. D., Fernández‐Villalba, E., & Herrero, M. T. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101204 · Cited by 14 · see citing works

Hypoxia Induces Alterations in the Circadian Rhythm in Patients with Chronic Respiratory Diseases

Castillejos-López, M. D. J., Romero, Y., Varela-Ordoñez, A., Flores‐Soto, E., Romero-Martínez, B. S., Velázquez‐Cruz, R., Vázquez-Pérez, J. A., Ruiz, V., Gómez-Verján, J. C., Rivero-Segura, N. A., et al. (2023) · Cells · doi:10.3390/cells12232724 · Cited by 13 · see citing works

Want of Wnt in Parkinson’s disease: Could sFRP disrupt interplay between Nurr1 and Wnt signaling?

Gamit, N., Dharmarajan, A., Sethi, G., & Warrier, S. R. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115566 · Cited by 13 · see citing works

Deletion of Wnt10a Is Implicated in Hippocampal Neurodegeneration in Mice

Zhang, J.-H., Tasaki, T., Tsukamoto, M., Wang, K., Kubo, K., & Azuma, K. (2022) · Biomedicines · doi:10.3390/biomedicines10071500 · Cited by 12 · see citing works

Age- and Sex-Associated Wnt Signaling Dysregulation is Exacerbated from the Early Stages of Neuropathology in an Alzheimer’s Disease Model

Colín-Martínez, E., la Fuente-Muñoz, C. E. D., & Arias, C. (2024) · Neurochemical Research · doi:10.1007/s11064-024-04224-7 · Cited by 8 · see citing works

Changes in Gene Expression Profile with Age in SAMP8: Identifying Transcripts Involved in Cognitive Decline and Sporadic Alzheimer’s Disease

Griñán‐Ferré, C., Servín-Muñoz, I. V., Palomera‐Ávalos, V., Martínez-Fernández, C., Companys‐Alemany, J., Muñoz-Villanova, A., Ortuño‐Sahagún, D., Pallàs, M., & Bellver‐Sanchís, A. (2024) · Genes · doi:10.3390/genes15111411 · Cited by 8 · see citing works

Age-dependent changes in Wnt signaling components and synapse number are differentially affected between brain regions

García‐Velázquez, L., López-Carrasco, P., & Arias, C. (2022) · Experimental Gerontology · doi:10.1016/j.exger.2022.111854 · Cited by 8 · see citing works

Primary cilia in Parkinson’s disease: summative roles in signaling pathways, genes, defective mitochondrial function, and substantia nigra dopaminergic neurons

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ApoE3 Christchurch and tau interaction as a protective mechanism against Alzheimer's disease

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