ArticleProceedings of the National Academy of Sciences of the United States of America2009
Intrahippocampal injection of a lentiviral vector expressing Nrf2 improves spatial learning in a mouse model of Alzheimer's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers.
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Who cites it
172 citing papers in PubMed, 290 citations in OpenAlex.
- 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
- Early astrocyte-targeted intervention guided byEuropean journal of nuclear medicine and molecular imaging · 2026Article
- Metabolic cell death networks in Alzheimer's disease: mechanistic links and therapeutic perspectives of ferroptosis, cuproptosis, and disulfidptosis.Frontiers in cell and developmental biology · 2026Review
- Exercise-induced modulation of astrocyte in Alzheimer's disease: mechanisms and therapeutic implications.Frontiers in physiology · 2026Review
- Discovery of a novel Keap1 inhibitor for neurodegeneration through virtual screening and molecular dynamics simulations.PloS one · 2026Article
- Impact and Significance of Viral Vectors for siRNA Delivery in the Treatment of Alzheimer's Disease.Current pharmaceutical biotechnology · 2026Review
- Slc22a17 governs postnatal neurogenesis by maintaining the iron homeostasis in hippocampus.Nature communications · 2025Article
- The Multi-Dimensional Action Map of Resveratrol Against Alzheimer's Disease: Mechanism Integration and Treatment Strategy Optimization.Nutrients · 2025Review
- Mechanism of Tiaogeng decoction in a cognitive dysfunction mouse model.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Benfotiamine Ameliorates Streptozotocin-Induced Alzheimer's Disease in Rats by Modulating Neuroinflammation, Oxidative Stress, and Microglia.Molecular neurobiology · 2025Article
- Exo70 Protects Against Memory and Synaptic Impairments Following Mild Traumatic Brain Injury.Antioxidants (Basel, Switzerland) · 2025Article
- Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases.Redox biology · 2025Review
- Identifying Specificity Protein 2 as a key marker for diabetic encephalopathy in the context of predictive, preventive, and personalized medicine.The EPMA journal · 2025Article
- diAcCA, a Pro-Drug for Carnosic Acid That Activates the Nrf2 Transcriptional Pathway, Shows Efficacy in the 5xFAD Transgenic Mouse Model of Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2025Article
- Review
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- Nrf2-Independent Anti-Inflammatory Effects of Dimethyl Fumarate: Challenges and Prospects in Developing Electrophilic Nrf2 Activators for Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- In vivo and ex vivo gene therapy for neurodegenerative diseases: a promise for disease modification.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
112 more citing papers are in PubMed but not listed here.
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11 authors at 2 institutions in 1 country.
Funding
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Abstract
The amyloid hypothesis of Alzheimer's disease (AD) postulates that amyloid-beta (Abeta) deposition and neurotoxicity play a causative role in AD; oxidative injury is thought to be central in the pathogenesis. An endogenous defense system against oxidative stress is induced by binding of the transcription factor nuclear factor E2-related factor 2 (Nrf2) to the antioxidant response element (ARE) enhancer sequence. The Nrf2-ARE pathway is activated in response to reactive oxygen species to trigger the simultaneous expression of numerous protective enzymes and scavengers. To exploit the Nrf2-ARE pathway therapeutically, we delivered Nrf2 bilaterally into the hippocampus of 9-month-old transgenic AD mice (APP/PS1 mice) using a lentiviral vector encoding human Nrf2. The data indicate that significant reductions in spatial learning deficits of aged APP/PS1 mice in a Morris Water Maze can be achieved by modulating levels of Nrf2 in the brain. Memory improvement in APP/PS1 mice after Nrf2 transduction shifts the balance between soluble and insoluble Abeta toward an insoluble Abeta pool without concomitant change in total brain Abeta burden. Nrf2 gene transfer is associated with a robust reduction in astrocytic but not microglial activation and induction of Nrf2 target gene heme oxygenase 1, indicating overall activation of the Nrf2-ARE pathway in hippocampal neurons 6 months after injection. Results warrant further exploration of the Nrf2-ARE pathway for treatment of AD and suggest that the Nrf2-ARE pathway may represent a potential therapeutic strategy to pursue in AD in humans, particularly in view of the multiple mechanisms by which Nrf2 can exert its protective effects.
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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.