ArticleNeurobiology of aging2012
A PIN1 polymorphism that prevents its suppression by AP4 associates with delayed onset of Alzheimer's disease.
Article in Neurobiology of aging, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 76 citations in OpenAlex.
- Association Between Alzheimer Disease and Cancer With Evaluation of Study Biases: A Systematic Review and Meta-analysis.JAMA network open · 2020Pooled it
- Viral Induced Oxidative and Inflammatory Response in Alzheimer's Disease Pathogenesis with Identification of Potential Drug Candidates: A Systematic Review using Systems Biology Approach.Current neuropharmacology · 2019Pooled it
- Cross-Talk Between Tau O-GlcNAcylation and the Formation of the Early Driver of Neurodegeneration (Cis P-Thr231-Pro Tau) in Primary Cortical Neurons.Molecular neurobiology · 2025Article
- Functional significance of some common oxytocin receptor SNPs involved in complex human traits.BMC molecular and cell biology · 2025Article
- The inverse association between cancer history and incident cognitive impairment: Addressing attrition bias.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Rapid Protein-Ligand Affinity Determination by Photoinduced Hyperpolarized NMR.Journal of the American Chemical Society · 2024Article
- Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery.Science signaling · 2024Review
- Polymorphism rs2327430 in TCF21 predicts the risk and prognosis of gastric cancer by affecting the binding between TFAP2A and TCF21.Cancer cell international · 2024Article
- Causal relationship between Alzheimer's disease and prostate cancer: a bidirectional Mendelian randomization analysis.Frontiers in endocrinology · 2024Article
- The role of the Pin1-Frontiers in cell and developmental biology · 2024Review
- Ultrafast Fragment Screening Using Photo-Hyperpolarized (CIDNP) NMR.Journal of the American Chemical Society · 2023Article
- Pin1 and Alzheimer's disease.Translational research : the journal of laboratory and clinical medicine · 2023Review
- Causal association between colorectal cancer and Alzheimer's disease: a bidirectional two-sample mendelian randomization study.Frontiers in genetics · 2023Article
- Cancer diagnosis is associated with a lower burden of dementia and less Alzheimer's-type neuropathology.Brain : a journal of neurology · 2022Article
- The Role of Dementia Diagnostic Delay in the Inverse Cancer-Dementia Association.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Article
- Targeting Pin1 for Modulation of Cell Motility and Cancer Therapy.Biomedicines · 2021Review
- The Peptidyl-prolyl Isomerase Pin1 in Neuronal Signaling: from Neurodevelopment to Neurodegeneration.Molecular neurobiology · 2021Review
- The Relationship Between Alzheimer's Disease and Skin Diseases: A Review.Clinical, cosmetic and investigational dermatology · 2021Review
- Oridonin Dose-Dependently Modulates the Cell Senescence and Apoptosis of Gastric Cancer Cells.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- The competing risk of death and selective survival cannot fully explain the inverse cancer-dementia association.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Alzheimer's disease (AD), the most common form of dementia, is characterized by the presence of neurofibrillary tangles composed of tau and senile plaques of amyloid-beta peptides (Aβ) derived from amyloid precursor protein (APP). Pin1 is a unique prolyl isomerase that has been shown to protect against age-dependent neurodegeneration by acting on phosphorylated tau and APP to suppress tangle formation and amyloidogenic APP processing. Here we report a functional polymorphism, rs2287839, in the Pin1 promoter that is significantly associated with a 3-year delay in the average age at onset (AAO) of late-onset AD in a Chinese population. More significantly, the Pin1 polymorphism rs2287839 is located within the consensus binding motif for the brain-selective transcription factor, AP4 (CAGCTG) and almost completely abolishes the ability of AP4 to bind and suppress the Pin1 promoter, as shown by chromatin immunoprecipitation, electrophoretic mobility shift assay, and promoter luciferase assay. Moreover, overexpression or knockdown of AP4 resulted in an 80% reduction or 2-fold increase in endogenous Pin1 levels, respectively. Thus, AP4 is a novel transcriptional repressor of Pin1 expression and the Pin1 promoter single nucleotide polymorphism (SNP) identified in this study that prevents such suppression is associated with delayed onset of AD. These results indicate that regulation of Pin1 by AP4 plays a critical role in determining age at onset of AD and might be a novel therapeutic target to delay the onset of AD.
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Registered trials
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