ArticleHuman molecular genetics2009
Suppression of GFAP toxicity by alphaB-crystallin in mouse models of Alexander disease.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- A systematic review and meta-analysis of GFAP gene variants in Alexander disease.Scientific reports · 2024Pooled it
- Progressive gait and motor deficits in a rat model of Alexander disease.Behavioural brain research · 2026Article
- Synergistic Effects of Glial Fibrillary Acidic Protein Mutation and Overexpression in the Pathogenesis of Alexander Disease.International journal of molecular sciences · 2026Article
- Article
- Development of perivascular astrocyte processes.Frontiers in neuroscience · 2025Review
- The Role of Small Heat Shock Proteins in Protein Misfolding Associated Motoneuron Diseases.International journal of molecular sciences · 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
- Crystallin Alpha-B Overexpression as a Possible Marker of Reactive Astrogliosis in Human Cerebral Contusions.Frontiers in cellular neuroscience · 2022Article
- Insights on Human Small Heat Shock Proteins and Their Alterations in Diseases.Frontiers in molecular biosciences · 2022Review
- Susceptibility of cytoskeletal-associated proteins for tumor progression.Cellular and molecular life sciences : CMLS · 2021Review
- Review
- The multicellular interplay of microglia in health and disease: lessons from leukodystrophy.Disease models & mechanisms · 2021Review
- Beneficial Effect of Phenytoin and Carbamazepine onFrontiers in pharmacology · 2021Article
- Immunomodulatory Effects of Dopamine in Inflammatory Diseases.Frontiers in immunology · 2021Review
- Alexander Disease Modeling in Zebrafish: An In Vivo System Suitable to Perform Drug Screening.Genes · 2020Article
- HspB5 protects mouse neural stem/progenitor cells from paraquat toxicity.American journal of stem cells · 2020Article
- Neuroproteomics in Epilepsy: What Do We Know so Far?Frontiers in molecular neuroscience · 2020Review
- Refining the concept of GFAP toxicity in Alexander disease.Journal of neurodevelopmental disorders · 2019Review
- Rapidly progressive amyotrophic lateral sclerosis is associated with microglial reactivity and small heat shock protein expression in reactive astrocytes.Neuropathology and applied neurobiology · 2019Article
- Advancing the pathologic phenotype of giant axonal neuropathy: early involvement of the ocular lens.Orphanet journal of rare diseases · 2019Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Alexander disease (AxD) is a primary disorder of astrocytes caused by dominant mutations in the gene for glial fibrillary acidic protein (GFAP). These mutations lead to protein aggregation and formation of Rosenthal fibers, complex astrocytic inclusions that contain GFAP, vimentin, plectin, ubiquitin, Hsp27 and alphaB-crystallin. The small heat shock protein alphaB-crystallin (Cryab) regulates GFAP assembly, and elevation of Cryab is a consistent feature of AxD; however, its role in Rosenthal fibers and AxD pathology is not known. Here, we show in AxD mouse models that loss of Cryab results in increased mortality, whereas elevation of Cryab rescues animals from terminal seizures. When mice with Rosenthal fibers induced by over-expression of GFAP are crossed into a Cryab-null background, over half die at 1 month of age. Restoration of Cryab expression through the GFAP promoter reverses this outcome, showing the effect is astrocyte-specific. Conversely, in mice engineered to express both AxD-associated mutations and elevated GFAP, which despite natural induction of Cryab also die at 1 month, transgenic over-expression of Cryab results in a markedly reduced CNS stress response, restores expression of the glutamate transporter Glt1 (EAAT2) and protects these animals from death. In its most common form, AxD is a devastating neurodegenerative disease, with early onset, characterized by seizures, spasticity and developmental delays, ultimately leading to death. Cryab plays a critical role in tempering AxD pathology and should be investigated as a therapeutic target for this and other diseases with astropathology.
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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.