ArticleJournal of neuroinflammation2007
Amyloid precursor protein modulates beta-catenin degradation.
Article in Journal of neuroinflammation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Low Levels of Amyloid Precursor Protein (APP) Promote Neurogenesis and Decrease Gliogenesis in Human Neural Stem Cells.International journal of molecular sciences · 2023Article
- Neurodevelopmental disorders and microcephaly: how apoptosis, the cell cycle, tau and amyloid-β precursor protein APPly.Frontiers in molecular neuroscience · 2023Review
- Role of Neddylation in Neurodegenerative Diseases.NeuroSci · 2022Review
- OLFML2A Downregulation Inhibits Glioma Proliferation Through Suppression of Wnt/β-Catenin Signaling.Frontiers in oncology · 2021Article
- Microglia and Wnt Pathways: Prospects for Inflammation in Alzheimer's Disease.Frontiers in aging neuroscience · 2020Review
- Restoring Wnt/β-catenin signaling is a promising therapeutic strategy for Alzheimer's disease.Molecular brain · 2019Review
- Novel Contribution of Secreted Amyloid-β Precursor Protein to White Matter Brain Enlargement in Autism Spectrum Disorder.Frontiers in psychiatry · 2019Review
- Mechanisms of Melatonin in Alleviating Alzheimer's Disease.Current neuropharmacology · 2017Review
- Novel roles of amyloid-beta precursor protein metabolites in fragile X syndrome and autism.Molecular psychiatry · 2016Review
- Finding novel distinctions between the sAPPα-mediated anabolic biochemical pathways in Autism Spectrum Disorder and Fragile X Syndrome plasma and brain tissue.Scientific reports · 2016Article
- Hippocampal Wnt3a is Necessary and Sufficient for Contextual Fear Memory Acquisition and Consolidation.Cerebral cortex (New York, N.Y. : 1991) · 2015Article
- Cycle on Wheels: Is APP Key to the AppBp1 Pathway?Austin Alzheimer's and Parkinson's disease · 2014Article
- The senescence hypothesis of disease progression in Alzheimer disease: an integrated matrix of disease pathways for FAD and SAD.Molecular neurobiology · 2013Review
- COPS5 (Jab1) protein increases β site processing of amyloid precursor protein and amyloid β peptide generation by stabilizing RanBP9 protein levels.The Journal of biological chemistry · 2013Article
- Canonical Wnt signaling is necessary for object recognition memory consolidation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Autism as early neurodevelopmental disorder: evidence for an sAPPα-mediated anabolic pathway.Frontiers in cellular neuroscience · 2013Article
- Neddylation dysfunction in Alzheimer's disease.Journal of cellular and molecular medicine · 2012Review
- Cul4B regulates neural progenitor cell growth.BMC neuroscience · 2012Article
- Autism, Alzheimer disease, and fragile X: APP, FMRP, and mGluR5 are molecular links.Neurology · 2011Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe amyloid precursor protein (APP) is genetically associated with Alzheimer's disease (AD). Elucidating the function of APP should help understand AD pathogenesis and provide insights into therapeutic designs against this devastating neurodegenerative disease.
resultsWe demonstrate that APP expression in primary neurons induces beta-catenin phosphorylation at Ser33, Ser37, and Thr41 (S33/37/T41) residues, which is a prerequisite for beta-catenin ubiquitinylation and proteasomal degradation. APP-induced phosphorylation of beta-catenin resulted in the reduction of total beta-catenin levels, suggesting that APP expression promotes beta-catenin degradation. In contrast, treatment of neurons with APP siRNAs increased total beta-catenin levels and decreased beta-catenin phosphorylation at residues S33/37/T41. Further, beta-catenin was dramatically increased in hippocampal CA1 pyramidal cells from APP knockout animals. Acute expression of wild type APP or of familial AD APP mutants in primary neurons downregulated beta-catenin in membrane and cytosolic fractions, and did not appear to affect nuclear beta-catenin or beta-catenin-dependent transcription. Conversely, in APP knockout CA1 pyramidal cells, accumulation of beta-catenin was associated with the upregulation of cyclin D1, a downstream target of beta-catenin signaling. Together, these data establish that APP downregulates beta-catenin and suggest a role for APP in sustaining neuronal function by preventing cell cycle reactivation and maintaining synaptic integrity.
conclusionWe have provided strong evidence that APP modulates beta-catenin degradation in vitro and in vivo. Future studies may investigate whether APP processing is necessary for beta-catenin downregulation, and determine if excessive APP expression contributes to AD pathogenesis through abnormal beta-catenin downregulation.
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Registered trials
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.