ArticleRedox biology2023
A potent phosphodiester Keap1-Nrf2 protein-protein interaction inhibitor as the efficient treatment of Alzheimer's disease.
Article in Redox biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 46 citations in OpenAlex.
- A novel Keap1-Nrf2 inhibitor 6K delays the progression of AKI-to-CKD by mitigating maladaptive repair.Redox biology · 2026Article
- Review
- Discovery of a novel Keap1 inhibitor for neurodegeneration through virtual screening and molecular dynamics simulations.PloS one · 2026Article
- Targeting ferroptosis with culinary spices: a dietary strategy for neuroprotection via the Nrf2/GPX4 axis.Frontiers in nutrition · 2026Review
- Atractylenolide III for central nervous system disorders: a review of multi-target mechanisms and therapeutic potential.Frontiers in pharmacology · 2026Review
- Caffeic acid alleviates myocardial ischemia-reperfusion injury by directly targeting Keap1Journal of pharmaceutical analysis · 2025Article
- Sensing within: Mitochondrial inside-out signal transduction.Cell chemical biology · 2025Review
- Chemical knockdown of Keap1 and homoPROTAC-ing allergic rhinitis.Acta pharmaceutica Sinica. B · 2025Article
- Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases.Redox biology · 2025Review
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- Oral iron sulfide prevents acute alcohol intoxication by initiating the endogenous multienzymatic antioxidant defense system.Science advances · 2025Article
- Acupuncture Ameliorates Alzheimer's-Like Cognitive Impairment and Pathological Changes via Regulating the Intestinal Fungal Community in APP/PS1 Mice.Neuropsychiatric disease and treatment · 2025Article
- Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies.Signal transduction and targeted therapy · 2024Review
- Neuroprotective effect of acetoxypachydiol against oxidative stress through activation of the Keap1-Nrf2/HO-1 pathway.BMC complementary medicine and therapies · 2024Article
- Understanding mechanisms of antioxidant action in health and disease.Nature reviews. Molecular cell biology · 2024Review
- γ-Secretase Inhibitors Selected by Molecular Docking, to Develop a New Drug Against Alzheimer's Disease.Reports of biochemistry & molecular biology · 2023Article
- The untapped potential of targeting NRF2 in neurodegenerative disease.Frontiers in aging · 2023Article
- Basal activation of astrocytic Nrf2 in neuronal culture media: Challenges and implications for neuron-astrocyte modelling.Brain and neuroscience advancesArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Keap1-Nrf2 pathway has been established as a therapeutic target for Alzheimer's disease (AD). Directly inhibiting the protein-protein interaction (PPI) between Keap1 and Nrf2 has been reported as an effective strategy for treating AD. Our group has validated this in an AD mouse model for the first time using the inhibitor 1,4-diaminonaphthalene NXPZ-2 with high concentrations. In the present study, we reported a new phosphodiester containing diaminonaphthalene compound, POZL, designed to target the PPI interface using a structure-based design strategy to combat oxidative stress in AD pathogenesis. Our crystallographic verification confirms that POZL shows potent Keap1-Nrf2 inhibition. Remarkably, POZL showed its high in vivo anti-AD efficacy at a much lower dosage compared to NXPZ-2 in the transgenic APP/PS1 AD mouse model. POZL treatment in the transgenic mice could effectively ameliorate learning and memory dysfunction by promoting the Nrf2 nuclear translocation. As a result, the oxidative stress and AD biomarker expression such as BACE1 and hyperphosphorylation of Tau were significantly reduced, and the synaptic function was recovered. HE and Nissl staining confirmed that POZL improved brain tissue pathological changes by enhancing neuron quantity and function. Furthermore, it was confirmed that POZL could effectively reverse Aβ-caused synaptic damage by activating Nrf2 in primary cultured cortical neurons. Collectively, our findings demonstrated that the phosphodiester diaminonaphthalene Keap1-Nrf2 PPI inhibitor could be regarded as a promising preclinical candidate of AD.
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.