ArticleThe Journal of biological chemistry2014
Nuclear translocation uncovers the amyloid peptide Aβ42 as a regulator of gene transcription.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Neurodegenerative Diseases: What Can Be Learned from Toothed Whales?Neuroscience bulletin · 2025Pooled it
- Restoration of Normal Occlusion Suppresses the Risk of Dementia.Neurochemical research · 2026Article
- Roles of RNA-Binding Nuclear Proteins in Alzheimer's Disease Pathophysiology.ACS pharmacology & translational science · 2026Review
- The mRNA Expression Levels of General Transcription Factors Altered in Alzheimer Cases Possibly Due to Amyloid Beta 1-42 Exposure.Noro psikiyatri arsivi · 2026Article
- Protein Kinases in Alzheimer's Disease: Pioneering Insights into Pathogenesis and Therapeutic Breakthroughs.Current neuropharmacology · 2026Review
- The CSF Levels of Mitochondrial Phosphoenolpyruvate Carboxykinase 2 as a Novel Biomarker in Alzheimer's Disease.Molecular neurobiology · 2025Article
- Impact of vitamin A on aged people's cognition and Alzheimer's disease progression in an animal model.NPJ science of food · 2025Article
- Nuclear pore dysfunction and disease: a complex opportunity.Nucleus (Austin, Tex.) · 2024Review
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- Interplay between APP and glypican-1 processing and α-synuclein aggregation in undifferentiated and differentiated human neural progenitor cells.Glycobiology · 2023Article
- Dendrimers and Derivatives as Multifunctional Nanotherapeutics for Alzheimer's Disease.Pharmaceutics · 2023Review
- A "grappling hook" interaction connects self-assembly and chaperone activity of Nucleophosmin 1.PNAS nexus · 2023Article
- Intraneuronal accumulation of amyloid-β peptides as the pathomechanism linking autism and its co-morbidities: epilepsy and self-injurious behavior - the hypothesis.Frontiers in molecular neuroscience · 2023Article
- Neurodevelopmental disorders and microcephaly: how apoptosis, the cell cycle, tau and amyloid-β precursor protein APPly.Frontiers in molecular neuroscience · 2023Review
- New Insights into lncRNAs in Aβ Cascade Hypothesis of Alzheimer's Disease.Biomolecules · 2022Review
- Could Amyloid-β 1-42 or α-Synuclein Interact Directly with Mitochondrial DNA? A Hypothesis.ACS chemical neuroscience · 2022Review
- Insulin-like growth factor 5 associates with human Aß plaques and promotes cognitive impairment.Acta neuropathologica communications · 2022Article
- Evaluation of Amyloid Inhibitor Efficiency to Block Bacterial Survival.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Alzheimer's Disease: A Molecular View of β-Amyloid Induced Morbific Events.Biomedicines · 2021Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although soluble species of the amyloid-β peptide Aβ42 correlate with disease symptoms in Alzheimer disease, little is known about the biological activities of amyloid-β (Aβ). Here, we show that Aβ peptides varying in lengths from 38 to 43 amino acids are internalized by cultured neuroblastoma cells and can be found in the nucleus. By three independent methods, we demonstrate direct detection of nuclear Aβ42 as follows: (i) biochemical analysis of nuclear fractions; (ii) detection of biotin-labeled Aβ in living cells by confocal laser scanning microscopy; and (iii) transmission electron microscopy of Aβ in cultured cells, as well as brain tissue of wild-type and transgenic APPPS1 mice (overexpression of amyloid precursor protein and presenilin 1 with Swedish and L166P mutations, respectively). Also, this study details a novel role for Aβ42 in nuclear signaling, distinct from the amyloid precursor protein intracellular domain. Chromatin immunoprecipitation showed that Aβ42 specifically interacts as a repressor of gene transcription with LRP1 and KAI1 promoters. By quantitative RT-PCR, we confirmed that mRNA levels of the examined candidate genes were exclusively decreased by the potentially neurotoxic Aβ42 wild-type peptide. Shorter peptides (Aβ38 or Aβ40) and other longer peptides (nontoxic Aβ42 G33A substitution or Aβ43) did not affect mRNA levels. Overall, our data indicate that the nuclear translocation of Aβ42 impacts gene regulation, and deleterious effects of Aβ42 in Alzheimer disease pathogenesis may be influenced by altering the expression profiles of disease-modifying genes.
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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.