ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Beneficial effects of Nrf2 overexpression in a mouse model of Alexander disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Progressive gait and motor deficits in a rat model of Alexander disease.Behavioural brain research · 2026Article
- 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
- Description of the Hamburg Alexander Leukodystrophy Cohort-Insights into Practical Classification and the Care Situation.Journal of clinical medicine · 2025Article
- A pure compound fromHeliyon · 2022Article
- Normal and Pathological NRF2 Signalling in the Central Nervous System.Antioxidants (Basel, Switzerland) · 2022Review
- Anastasis Drives Senescence and Non-Cell Autonomous Neurodegeneration in the Astrogliopathy Alexander Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- The NRF2-Dependent Transcriptional Regulation of Antioxidant Defense Pathways: Relevance for Cell Type-Specific Vulnerability to Neurodegeneration and Therapeutic Intervention.Antioxidants (Basel, Switzerland) · 2021Review
- Pexidartinib treatment in Alexander disease model mice reduces macrophage numbers and increases glial fibrillary acidic protein levels, yet has minimal impact on other disease phenotypes.Journal of neuroinflammation · 2021Article
- Astrocyte-specific overexpression of Nrf2 protects against optic tract damage and behavioural alterations in a mouse model of cerebral hypoperfusion.Scientific reports · 2018Article
- Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms.Acta neuropathologica · 2017Review
- Glial fibrillary acidic protein exhibits altered turnover kinetics in a mouse model of Alexander disease.The Journal of biological chemistry · 2017Article
- Role of major and brain-specific Sgce isoforms in the pathogenesis of myoclonus-dystonia syndrome.Neurobiology of disease · 2017Article
- Alexander Disease Mutations Produce Cells with Coexpression of Glial Fibrillary Acidic Protein and NG2 in Neurosphere Cultures and Inhibit Differentiation into Mature Oligodendrocytes.Frontiers in neurology · 2017Article
- Adaptive regulation of the brain's antioxidant defences by neurons and astrocytes.Free radical biology & medicine · 2016Review
- High-Throughput Screening for Drugs that Modulate Intermediate Filament Proteins.Methods in enzymology · 2016Article
- Nitric oxide mediates glial-induced neurodegeneration in Alexander disease.Nature communications · 2015Article
- Tuscan black kale sprout extract bioactivated with myrosinase: a novel natural product for neuroprotection by inflammatory and oxidative response during cerebral ischemia/reperfusion injury in rat.BMC complementary and alternative medicine · 2015Article
- Exploiting metabolic and antioxidant pathways to maintain vision in blinding disease.The Journal of clinical investigation · 2015Article
- Lithium Decreases Glial Fibrillary Acidic Protein in a Mouse Model of Alexander Disease.PloS one · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Alexander disease is a fatal neurodegenerative disease caused by dominant mutations in glial fibrillary acidic protein (GFAP). The disease is characterized by protein inclusions called Rosenthal fibers within astrocyte cell bodies and processes, and an antioxidant response mediated by the transcription factor Nrf2. We sought to test whether further elevation of Nrf2 would be beneficial in a mouse model of Alexander disease. Forcing overexpression of Nrf2 in astrocytes of R236H GFAP mutant mice decreased GFAP protein in all brain regions examined (olfactory bulb, hippocampus, cerebral cortex, brainstem, cerebellum, and spinal cord) and decreased Rosenthal fibers in olfactory bulb, hippocampus, corpus callosum, and brainstem. Nrf2 overexpression also restored body weights of R236H mice to near wild-type levels. Nrf2 regulates several genes involved in homeostasis of the antioxidant molecule glutathione, and the neuroprotective effects of Nrf2 in other neurological disorders may reflect restoration of glutathione to normal levels. However, glutathione levels in R236H mice were not decreased. Nrf2 overexpression did not change glutathione levels or ratio of reduced to oxidized glutathione (indicative of oxidative stress) in olfactory bulb, where Nrf2 dramatically reduced GFAP. Depletion of glutathione through knock-out of the GCLM (glutamate-cysteine ligase modifier subunit) also did not affect GFAP levels or body weight of R236H mice. These data suggest that the beneficial effects of Nrf2 are not mediated through glutathione.
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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.