ArticleMolecular neurobiology2023
Suppression of Wnt/β-Catenin Signaling Is Associated with Downregulation of Wnt1, PORCN, and Rspo2 in Alzheimer's Disease.
Article in Molecular neurobiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Discovery of a CI-994 derivative as a dual modulator of class I HDACs and Wnt/β- catenin signaling for Alzheimer's disease therapy.bioRxiv : the preprint server for biology · 2026Article
- Association of Wnt1, PORCN, RSPO2 and neuroinflammation with cognitive impairment, depression and quality of life in type 2 diabetes mellitus: a case-control study.Metabolic brain disease · 2026Article
- Lithium chloride suppresses ferroptosis of induced pluripotent stem cells with ApoE4/E4 from a sporadic Alzheimer's disease patient.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Serum Levels of Wnt/β-catenin Pathway Regulators Dkk-1, PORCN, Notum, and Tiki-1 in Children with Autism Spectrum Disorder.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026Article
- CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Extracellular Vesicles in Alzheimer's Disease: Dual Roles in Pathogenesis, Promising Avenues for Diagnosis and Therapy.Pharmaceutics · 2026Review
- Association Between Gene Polymorphisms of RSPO2 of the Wnt Signaling Pathway and Schizophrenia in the Korean Population.Psychiatry investigation · 2025Article
- Comprehensive and In-Depth Molecular and Pathway Studies of the Hippocampus in Alzheimer's Disease.Cellular and molecular neurobiology · 2025Article
- The Synergistic Role of ApoE4 and GSK3β in Alzheimer's Disease: Pathological Mechanisms and Therapeutic Implications.Molecular neurobiology · 2025Review
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Unlocking Hope: Therapeutic Advances and Approaches in Modulating the Wnt Pathway for Neurodegenerative Diseases.Molecular neurobiology · 2025Review
- Myeloid ectopic viral integration site 2 accelerates the progression of Alzheimer's disease.Aging cell · 2024Article
- APOE deficiency impacts neural differentiation and cholesterol biosynthesis in human iPSC-derived cerebral organoids.Stem cell research & therapy · 2023Article
- The role of Evi/Wntless in exporting Wnt proteins.Development (Cambridge, England) · 2023Review
- Upregulation of sFRP1 Is More Profound in Female than Male 5xFAD Mice and Positively Associated with Amyloid Pathology.Journal of Alzheimer's disease : JAD · 2023Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Wnt and R-spondin (Rspo) proteins are two major types of endogenous Wnt/β-catenin signaling agonists. While Wnt/β-catenin signaling is greatly diminished in Alzheimer's disease (AD), it remains to be elucidated whether the inhibition of this pathway is associated with dysregulation of Wnt and Rspo proteins. By analyzing temporal cortex RNA-seq data of the human postmortem brain samples, we found that WNT1 and RRPO2 were significantly downregulated in human AD brains. In addition, the expression of Wnt acyltransferase porcupine (PORCN), which is essential for Wnt maturation and secretion, was greatly deceased in these human AD brains. Interestingly, the lowest levels of WNT1, PORCN, and RSPO2 expression were found in human AD brains carrying two copies of APOE4 allele, the strongest genetic risk factor of late-onset AD. Importantly, there were positive correlations among the levels of WNT1, PORCN, and RSPO2 expression in human AD brains. Supporting observations in humans, Wnt1, PORCN, and Rspo2 were downregulated and Wnt/β-catenin signaling was diminished in the 5xFAD amyloid model mice. In human APOE-targeted replacement mice, downregulation of WNT1, PORCN, and RSPO2 expression was positively associated with aging and APOE4 genotype. Finally, WNT1 and PORCN expression and Wnt/β-catenin signaling were inhibited in human APOE4 iPSC-derived astrocytes when compared to the isogenic APOE3 iPSC-derived astrocytes. Altogether, our findings suggest that the dysregulations of Wnt1, PORCN, and Rspo2 could be coordinated together to diminish Wnt/β-catenin signaling in aging- and APOE4-dependent manners in the AD brain.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.