ArticleNature communications2016
Regulation of PERK-eIF2α signalling by tuberous sclerosis complex-1 controls homoeostasis and survival of myelinating oligodendrocytes.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers.
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
37 citing papers in PubMed, 54 citations in OpenAlex.
- Effects of Anesthesia Neurotoxicity on Oligodendrocyte Development and Myelination: An In Vitro Study Using Primary Cultures.International journal of molecular sciences · 2026Article
- Myelin dysfunction in autism spectrum disorder: insights into core symptoms and mechanisms of brain development.Molecular psychiatry · 2026Review
- ENT1 inhibitor J4 restores cognitive function and white-matter integrity in a mouse model of tuberous sclerosis complex.Journal of biomedical science · 2026Article
- Repeated sevoflurane exposure causes hypomyelination in the prefrontal cortex of adult male mice.Scientific reports · 2025Article
- Development of Oligodendroglia and Myelin.Advances in neurobiology · 2025Review
- ISR Modulators in Neurological Diseases.Current neuropharmacology · 2025Review
- Potential Role of Endoplasmic Reticulum Stress in Modulating Protein Homeostasis in Oligodendrocytes to Improve White Matter Injury in Preterm Infants.Molecular neurobiology · 2024Review
- The role of TSC1 and TSC2 proteins in neuronal axons.Molecular psychiatry · 2024Review
- Modeling tuberous sclerosis complex with human induced pluripotent stem cells.World journal of pediatrics : WJP · 2024Review
- The AMPK activator metformin improves recovery from demyelination by shifting oligodendrocyte bioenergetics and accelerating OPC differentiation.Frontiers in cellular neuroscience · 2023Article
- A Glance at the Molecules That Regulate Oligodendrocyte Myelination.Current issues in molecular biology · 2022Review
- Identifying oligodendrocyte enhancers governing Plp1 expression.Human molecular genetics · 2021Article
- Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma.Scientific reports · 2021Article
- The Akt-mTOR Pathway Drives Myelin Sheath Growth by Regulating Cap-Dependent Translation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Pathological Features of Tumors of the Nervous System in Hereditary Cancer Predisposition Syndromes: A Review.Neurosurgery · 2021Review
- Intrinsic and extrinsic regulators of oligodendrocyte progenitor proliferation and differentiation.Seminars in cell & developmental biology · 2021Article
- Article
- Premyelinating Oligodendrocytes: Mechanisms Underlying Cell Survival and Integration.Frontiers in cell and developmental biology · 2021Review
- The paradox of autophagy in Tuberous Sclerosis Complex.Genetics and molecular biology · 2021Article
- Oligodendrocyte-Specific Mechanisms of Myelin Thinning: Implications for Neurodegenerative Diseases.Frontiers in neuroscience · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
Tuberous sclerosis complex-1 or 2 (TSC1/2) mutations cause white matter abnormalities, including myelin deficits in the CNS; however, underlying mechanisms are not fully understood. TSC1/2 negatively regulate the function of mTOR, which is required for oligodendrocyte differentiation. Here we report that, unexpectedly, constitutive activation of mTOR signalling by Tsc1 deletion in the oligodendrocyte lineage results in severe myelination defects and oligodendrocyte cell death in mice, despite an initial increase of oligodendrocyte precursors during early development. Expression profiling analysis reveals that Tsc1 ablation induces prominent endoplasmic reticulum (ER) stress responses by activating a PERK-eIF2α signalling axis and Fas-JNK apoptotic pathways. Enhancement of the phospho-eIF2α adaptation pathway by inhibition of Gadd34-PP1 phosphatase with guanabenz protects oligodendrocytes and partially rescues myelination defects in Tsc1 mutants. Thus, TSC1-mTOR signalling acts as an important checkpoint for maintaining oligodendrocyte homoeostasis, pointing to a previously uncharacterized ER stress mechanism that contributes to hypomyelination in tuberous sclerosis.
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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.