ArticleNeurotoxicology2012
Activation of the Nrf2-ARE pathway by siRNA knockdown of Keap1 reduces oxidative stress and provides partial protection from MPTP-mediated neurotoxicity.
Article in Neurotoxicology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Solvents and Parkinson disease: a systematic review of toxicological and epidemiological evidence.Toxicology and applied pharmacology · 2013Pooled it
- Ferroptosis in Parkinson's disease: a review of molecular mechanisms and emerging therapeutic strategies.Frontiers in neuroscience · 2026Review
- Aqueous Extract ofInternational journal of molecular sciences · 2025Article
- shRNA-interfered of Nrf2 reveals a critical role for Keap1-Nrf2 signaling pathway during effects of zearalenone induced oxidative stress in IPEC-J2 cells.Animal bioscience · 2025Article
- Traditional Chinese medicine in the treatment ofWorld journal of gastroenterology · 2025Review
- The Bioactive Gamma-Oryzanol fromAntioxidants (Basel, Switzerland) · 2024Article
- Role of Astrogliosis in the Pathogenesis of Parkinson's Disease: Insights into Astrocytic Nrf2 Pathway as a Potential Therapeutic Target.CNS & neurological disorders drug targets · 2024Review
- Targeting the NRF2 pathway for disease modification in neurodegenerative diseases: mechanisms and therapeutic implications.Frontiers in pharmacology · 2024Review
- Therapeutic Potential of Capsaicin in Various Neurodegenerative Diseases with Special Focus on Nrf2 Signaling.Current pharmaceutical biotechnology · 2024Review
- Proximity proteomic analysis of the NRF family reveals the Parkinson's disease protein ZNF746/PARIS as a co-complexed repressor of NRF2.Science signaling · 2023Article
- Targeting Nrf2 signaling pathway and oxidative stress by resveratrol for Parkinson's disease: an overview and update on new developments.Molecular biology reports · 2023Review
- Mitochondrial Medicine: A Promising Therapeutic Option Against Various Neurodegenerative Disorders.Current neuropharmacology · 2023Review
- Antisense oligonucleotides: a novel Frontier in pharmacological strategy.Frontiers in pharmacology · 2023Review
- The untapped potential of targeting NRF2 in neurodegenerative disease.Frontiers in aging · 2023Article
- Pathogenesis of α-Synuclein in Parkinson's Disease: From a Neuron-Glia Crosstalk Perspective.International journal of molecular sciences · 2022Review
- The use of fibroblasts as a valuable strategy for studying mitochondrial impairment in neurological disorders.Translational neurodegeneration · 2022Review
- Nrf2/Keap1/ARE signaling: Towards specific regulation.Life sciences · 2022Review
- UsingFrontiers in pharmacology · 2022Review
- Glial Purinergic Signaling-Mediated Oxidative Stress (GPOS) in Neuropsychiatric Disorders.Oxidative medicine and cellular longevity · 2022Review
- An Overview of the Nrf2/ARE Pathway and Its Role in Neurodegenerative Diseases.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that binds to the antioxidant response element, a cis-acting regulatory element that increases expression of detoxifying enzymes and antioxidant proteins. Kelch-like ECH associating protein 1 (Keap1) protein is a negative regulator of Nrf2. Previous work has shown that genetic overexpression of Nrf2 is protective in vitro and in vivo. To modulate the Nrf2-ARE system without overexpressing Nrf2, we used short interfering RNA (siRNA) directed against Keap1. Keap1 siRNA administration in primary astrocytes increased the levels of Nrf2-ARE driven genes and protected against oxidative stress. Moreover, Keap1 siRNA resulted in a persistent upregulation of the Nrf2-ARE pathway and protection against oxidative stress in primary astrocytes. Keap1 siRNA injected into the striatum was also modestly protective against MPTP-induced dopaminergic terminal damage. These data indicate that activation of endogenous intracellular levels of Nrf2 is sufficient to protect in models of oxidative stress and Parkinson's disease.
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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 OpenQuestion graph.