ArticleNeuromolecular medicine2014
Multiple mechanisms of iron-induced amyloid beta-peptide accumulation in SHSY5Y cells: protective action of negletein.
Article in Neuromolecular medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Small-Molecule Targeting of the Iron-Responsive Element in the APP mRNA 5'-UTR to Control Amyloid Translation in Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Reexamining the Role of Amyloid β Clearance from the Brain: Exporting Labile Iron from the Interstitial Fluid Performs a Protective Function.International journal of molecular sciences · 2026Review
- Dimethyl-2-oxoglutarate but not antioxidants prevents glucose hypometabolism induced neural cell death: implications in the pathogenesis and therapy of Alzheimer's disease.Biochemistry and biophysics reports · 2025Article
- Iron-Mediated Overexpression of Amyloid Precursor Protein via Iron Responsive mRNA in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Ferric Ammonium Citrate Reduces Claudin-5 Abundance and Function in Primary Mouse Brain Endothelial Cells.Pharmaceutical research · 2025Article
- Effects of mixed metal exposures on MRI diffusion features in the medial temporal lobe.Neurotoxicology · 2024Article
- The Irony of Iron: The Element with Diverse Influence on Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Effects of mixed metal exposures on MRI diffusion features in the medial temporal lobe.medRxiv : the preprint server for health sciences · 2024Article
- Higher hippocampal diffusivity values in welders are associated with greater R2* in the red nucleus and lower psychomotor performance.Neurotoxicology · 2023Article
- Role of Metal Cations of Copper, Iron, and Aluminum and Multifunctional Ligands in Alzheimer's Disease: Experimental and Computational Insights.ACS omega · 2023Review
- Dysregulation of Neuronal Iron in Alzheimer's Disease.Current neuropharmacology · 2023Article
- Unveiling the Potential of Polyphenols as Anti-Amyloid Molecules in Alzheimer's Disease.Current neuropharmacology · 2023Review
- Lysine-targeting inhibition of amyloid β oligomerization by a green perilla-derived metastable chalconeRSC chemical biology · 2022Article
- Biological Potential, Gastrointestinal Digestion, Absorption, and Bioavailability of Algae-Derived Compounds with Neuroprotective Activity: A Comprehensive Review.Marine drugs · 2022Review
- Neuropathological Mechanisms of β-N-Methylamino-L-Alanine (BMAA) with a Focus on Iron Overload and Ferroptosis.Neurotoxicity research · 2022Review
- Oxidative Stress and Beta Amyloid in Alzheimer's Disease. Which Comes First: The Chicken or the Egg?Antioxidants (Basel, Switzerland) · 2021Review
- Regional brain iron associated with deterioration in Alzheimer's disease: A large cohort study and theoretical significance.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Article
- Review
- The Role of Butyrylcholinesterase and Iron in the Regulation of Cholinergic Network and Cognitive Dysfunction in Alzheimer's Disease Pathogenesis.International journal of molecular sciences · 2021Review
- Glycyl-L-Prolyl-L-Glutamate Pseudotripeptides for Treatment of Alzheimer's Disease.Biomolecules · 2021Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The increased accumulation of iron in the brain in Alzheimer's disease (AD) is well documented, and excess iron is strongly implicated in the pathogenesis of the disease. The adverse effects of accumulated iron in AD brain may include the oxidative stress, altered amyloid beta-metabolism and the augmented toxicity of metal-bound amyloid beta 42. In this study, we have shown that exogenously added iron in the form of ferric ammonium citrate (FAC) leads to considerable accumulation of amyloid precursor protein (APP) without a corresponding change in the concerned gene expression in cultured SHSY5Y cells during exposure up to 48 h. This phenomenon is also associated with increased β-secretase activity and augmented release of amyloid beta 42 in the medium. Further, the increase in β-secretase activity, in SHSY5Y cells, upon exposure to iron apparently involves reactive oxygen species (ROS) and NF-κB activation. The synthetic flavone negletein (5,6-dihydroxy-7-methoxyflavone), which is a known chelator for iron, can significantly prevent the effects of FAC on APP metabolism in SHSY5Y cells. Further, this compound inhibits the iron-dependent formation of ROS and also blocks the iron-induced oligomerization of amyloid beta 42 in vitro. In concentrations used in this study, negletein alone appears to have only marginal toxic effects on cell viability, but, on the other hand, the drug is capable of ameliorating the iron-induced loss of cell viability considerably. Our results provide the initial evidence of potential therapeutic effects of negletein, which should be explored in suitable animal models of AD.
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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.