ArticleToxicological sciences : an official journal of the Society of Toxicology2010
Astrocyte-specific overexpression of Nrf2 protects striatal neurons from mitochondrial complex II inhibition.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 82 citations in OpenAlex.
- Neuronal overexpression of Nrf2 reduces dystrophic neurites in 5XFAD Alzheimer's disease model mice.Alzheimer's research & therapy · 2026Article
- Neuronal overexpression of Nrf2 reduces dystrophic neurites in 5XFAD Alzheimer's disease model mice.bioRxiv : the preprint server for biology · 2026Article
- Chlorogenic Acid Alleviates the Detrimental Effects of Concurrent Hyperglycemia and Chronic Stress on Brain Homeostasis by Modulating Antioxidative Defense in Adult Zebrafish.Antioxidants (Basel, Switzerland) · 2025Article
- Aβ Deposition in Extracellular Space Disrupts Glial-Neuron Communication and Triggers Alzheimer's Disease.Aging and disease · 2025Review
- Multitarget Effects of Nrf2 Signalling in the Brain: Common and Specific Functions in Different Cell Types.Antioxidants (Basel, Switzerland) · 2024Review
- Role of the transcription factor NRF2 in maintaining the integrity of the Blood-Brain Barrier.Fluids and barriers of the CNS · 2024Review
- NRF2 in age-related musculoskeletal diseases: Role and treatment prospects.Genes & diseases · 2024Review
- A phenotypic screening platform for identifying chemical modulators of astrocyte reactivity.Nature neuroscience · 2024Article
- Review
- Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.Archives of toxicology · 2024Review
- The cell-specific roles of Nrf2 in acute and chronic phases of ischemic stroke.CNS neuroscience & therapeutics · 2024Review
- Effect of Nrf2 on brain injury induced by hydraulic shock via regulation of mitophagy and apoptosis.Aging · 2023Article
- Nrf2 is predominantly expressed in hippocampal neurons in a rat model of temporal lobe epilepsy.Cell & bioscience · 2023Article
- Review
- Neuroinflammation in Huntington's Disease: A Starring Role for Astrocyte and Microglia.Current neuropharmacology · 2022Review
- α-Synuclein pathology in Parkinson disease activates homeostatic NRF2 anti-oxidant response.Acta neuropathologica communications · 2021Article
- Mitochondria as the memory of preconditioning.Conditioning medicine · 2021Article
- Antioxidants and Neuron-Astrocyte Interplay in Brain Physiology: Melatonin, a Neighbor to Rely on.Neurochemical research · 2021Review
- Nrf2 Overexpression for the Protective Effect of Skin-Derived Precursors against UV-Induced Damage: Evidence from a Three-Dimensional Skin Model.Oxidative medicine and cellular longevity · 2019Article
- Quinolinic Acid and Nuclear Factor Erythroid 2-Related Factor 2 in Depression: Role in Neuroprogression.Frontiers in pharmacology · 2019Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that is known to regulate a variety of cytoprotective genes through the antioxidant response element (ARE). This endogenous response is one of the major pathways by which cells are protected from xenobiotic or innate oxidative insults. Furthermore, in neural systems, astrocyte-specific activation of Nrf2 is known to protect neurons. In previous work, our laboratory found that Nrf2 protects from intrastriatal injections of the mitochondrial complex II inhibitor malonate. Here, we extend these results to show that multiple methods of astrocyte-specific Nrf2 overexpression provide protection from neurotoxicity in vivo. GFAP-Nrf2 transgenic mice are significantly more resistant to malonate lesioning. This outcome is associated with an increased basal resistance, but more so, an enhanced Nrf2 response to lesioning that attenuated the ensuing neurotoxicity. Furthermore, striatal transplantation of neuroprogenitor cells overexpressing Nrf2 that differentiate into astrocytes after grafting also significantly reduced malonate toxicity. Overall, these data establish that enhanced astrocytic Nrf2 response and Nrf2 preconditioning are both sufficient to protect from acute lesions from mitochondrial complex II inhibition.
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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.