ArticleJournal of cellular and molecular medicine2009
Flavonoid-mediated presenilin-1 phosphorylation reduces Alzheimer's disease beta-amyloid production.
Article in Journal of cellular and molecular medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT01716637 (Open Label,Crossover,Pilot Study to Assess the Efficacy & Safety of Perispinal Admin.of Etanercept), which is not on this map. Cited by 68 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Open Label,Crossover,Pilot Study to Assess the Efficacy & Safety of Perispinal Admin.of Etanercept(Enbrel®) in Comb.w/Nutritional Supplements vs. Nutritional Supplements Alone in Subj. w/Mild to Mod. Alzheimer's Disease Receiving Std. Care.
Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.
- Genetics of COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review.Annals of clinical and translational neurology · 2022Pooled it
- Network Pharmacology-Based Analysis Reveals the Mechanisms of the Tibetan Medicinal PlantCurrent issues in molecular biology · 2026Article
- Phytoconstituents as Potential Therapeutics against Enzymatic Targets for Neurodegenerative Diseases.Current protein & peptide science · 2026Review
- Luteolin in Safflower Leaves Suppresses Microglial Inflammation Through FOXO3-MediatedAntioxidants (Basel, Switzerland) · 2025Article
- Modulation of nitric oxide signaling by flavonoids: implications for neurodegeneration.Molecular biology reports · 2025Review
- Multi-targeted approach via apigenin-7-O-glucoside for therapeutic intervention of Tau phosphorylating kinases in Alzheimer's disease.3 Biotech · 2025Article
- Article
- Glycogen synthase kinase 3 (GSK3) inhibition: a potential therapeutic strategy for Alzheimer's disease.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Therapeutic Expedition of Luteolin against Brain-related Disorders: An Updated Review.Combinatorial chemistry & high throughput screening · 2025Review
- The neuroprotective effects of hesperidin and diosmin in neurological disorders via targeting various signaling pathways.Iranian journal of basic medical sciences · 2025Review
- Luteolin for neurodegenerative diseases: a review.Pharmacological reports : PR · 2024Review
- Mast Cells in Autism Spectrum Disorder-The Enigma to Be Solved?International journal of molecular sciences · 2024Review
- The role of natural flavonoids on neuroinflammation as a therapeutic target for Alzheimer's disease: a narrative review.Neural regeneration research · 2023Review
- Anti-Neurodegenerating Activity: Structure-Activity Relationship Analysis of Flavonoids.Molecules (Basel, Switzerland) · 2023Article
- Comprehensive Review of Nutraceuticals against Cognitive Decline Associated with Alzheimer's Disease.ACS omega · 2023Review
- Neuroprotective Potential of Flavonoids in Brain Disorders.Brain sciences · 2023Review
- Potential Role of Moesin in Regulating Mast Cell Secretion.International journal of molecular sciences · 2023Review
- Apitherapy in Post-Ischemic Brain Neurodegeneration of Alzheimer's Disease Proteinopathy: Focus on Honey and Its Flavonoids and Phenolic Acids.Molecules (Basel, Switzerland) · 2023Review
- Aged brain and neuroimmune responses to COVID-19: post-acute sequelae and modulatory effects of behavioral and nutritional interventions.Immunity & ageing : I & A · 2023Review
- A Scientometric Study to a Critical Review on Promising Anticancer and Neuroprotective Compounds: Citrus Flavonoids.Antioxidants (Basel, Switzerland) · 2023Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Glycogen synthase kinase 3 (GSK-3) dysregulation is implicated in the two Alzheimer's disease (AD) pathological hallmarks: beta-amyloid plaques and neurofibrillary tangles. GSK-3 inhibitors may abrogate AD pathology by inhibiting amyloidogenic gamma-secretase cleavage of amyloid precursor protein (APP). Here, we report that the citrus bioflavonoid luteolin reduces amyloid-beta (Abeta) peptide generation in both human 'Swedish' mutant APP transgene-bearing neuron-like cells and primary neurons. We also find that luteolin induces changes consistent with GSK-3 inhibition that (i) decrease amyloidogenic gamma-secretase APP processing, and (ii) promote presenilin-1 (PS1) carboxyl-terminal fragment (CTF) phosphorylation. Importantly, we find GSK-3alpha activity is essential for both PS1 CTF phosphorylation and PS1-APP interaction. As validation of these findings in vivo, we find that luteolin, when applied to the Tg2576 mouse model of AD, decreases soluble Abeta levels, reduces GSK-3 activity, and disrupts PS1-APP association. In addition, we find that Tg2576 mice treated with diosmin, a glycoside of a flavonoid structurally similar to luteolin, display significantly reduced Abeta pathology. We suggest that GSK-3 inhibition is a viable therapeutic approach for AD by impacting PS1 phosphorylation-dependent regulation of amyloidogenesis.
Indexed as
Identifiers
What OpenQuestion holds
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.