ArticleHuman molecular genetics2017
Genetic reduction of Nrf2 exacerbates cognitive deficits in a mouse model of Alzheimer's disease.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 139 citations in OpenAlex.
- Oligodendrocyte dysfunction in human age-related cognitive decline.Nature medicine · 2026Article
- Exercise-Driven NRF2 Activation as a Systemic Neuroprotective Strategy: Integrating Redox Biology, Muscle-Brain Crosstalk, and Therapeutic Targeting in Neurodegeneration.Biochemical genetics · 2026Review
- Beyond KEAP1: The Context-Specific NRF2 Partner Code in Disease and Therapy.Antioxidants (Basel, Switzerland) · 2026Review
- Neuronal overexpression of Nrf2 reduces dystrophic neurites in 5XFAD Alzheimer's disease model mice.Alzheimer's research & therapy · 2026Article
- NRF2 deficit prevents pathologic Tau seeding and spreading in an induced tauopathy mouse model.Redox biology · 2026Article
- Neuronal overexpression of Nrf2 reduces dystrophic neurites in 5XFAD Alzheimer's disease model mice.bioRxiv : the preprint server for biology · 2026Article
- Article
- Simufilam in Alzheimer's Disease: Assessment of Efficacy of a Controversial Drug in Human Neuronal Cell Culture.Pharmaceuticals (Basel, Switzerland) · 2026Article
- LRRK2 kinase activity restricts NRF2-dependent mitochondrial protection in microglia.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Phytomedicines in preclinical and clinical research on antipsychotics-induced EPS/EPS-like behaviors: therapeutic effects and neurobiological mechanisms.Frontiers in psychiatry · 2026Review
- Micro- and Nanoplastics and Functional Nutrients in Human Health: Epigenetic Mechanisms and Cellular Resilience Signaling in Brain Insulin Resistance and the Risk of Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Slc22a17 governs postnatal neurogenesis by maintaining the iron homeostasis in hippocampus.Nature communications · 2025Article
- Bicyclol improves cognition deficits and inhibits oxidative stress-induced neuronal cell apoptosis in alzheimer's disease via Nrf2/HO-1 pathway.Metabolic brain disease · 2025Article
- Ceramides may Play a Central Role in the Pathogenesis of Alzheimer's Disease: a Review of Evidence and Horizons for Discovery.Molecular neurobiology · 2025Review
- Fermented Soybean Pulp Alleviates Disease Progression of 5×FAD Model Mice.Molecular neurobiology · 2025Article
- Alzheimer's Disease Pathogenic Mechanisms: Linking Redox Homeostasis and Mitochondria-Associated Metabolic Pathways Through Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2).Antioxidants (Basel, Switzerland) · 2025Review
- VILIP3 attenuates neuronal apoptosis and oxidative stress via Nrf2 activation in the pathogenesis of Alzheimer's disease.Molecular medicine (Cambridge, Mass.) · 2025Article
- The Conceivable Role of Metabolic Syndrome in the Pathogenesis of Alzheimer's Disease: Cellular and Subcellular Alterations in Underpinning a Tale of Two.Neuromolecular medicine · 2025Review
- A positron emission tomography tracer for the imaging of oxidative stress in the central nervous system.Nature biomedical engineering · 2025Article
- Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases.Redox biology · 2025Review
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Aging is the major risk factor for several neurodegenerative diseases, including Alzheimer's disease (AD). However, the mechanisms by which aging contributes to neurodegeneration remain elusive. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor that regulates expression of a vast number of genes by binding to the antioxidant response element. Nrf2 levels decrease as a function of age, and reduced Nrf2 levels have been reported in postmortem human brains and animal models of AD. Nevertheless, it is still unknown whether Nrf2 plays a role in the cognitive deficits associated with AD. To address this question, we used a genetic approach to remove the Nrf2 gene from APP/PS1 mice, a widely used animal model of AD. We found that the lack of Nrf2 significantly exacerbates cognitive deficits in APP/PS1, without altering gross motor function. Specifically, we found an exacerbation of deficits in spatial learning and memory, as well as in working and associative memory. Different brain regions control these behavioral tests, indicating that the lack of Nrf2 has a global effect on brain function. The changes in cognition were linked to an increase in Aβ and interferon-gamma (IFNγ) levels, and microgliosis. The changes in IFNγ levels are noteworthy as previously published evidence indicates that IFNγ can increase microglia activation and induce Aβ production. Our data suggest a clear link between Nrf2 and AD-mediated cognitive decline and further strengthen the connection between Nrf2 and AD.
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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 Socratic graph.