ArticleCell reports2017
Aberrant Proteostasis of BMAL1 Underlies Circadian Abnormalities in a Paradigmatic mTOR-opathy.
Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Clock gene dysregulation in epilepsy: A systematic review.Epilepsia open · 2026Pooled it
- Circadian synchronization between diet and gut microbiota in modulating host's health.Gut microbes · 2026Review
- mTOR signaling contributes to system-driven rhythmic gene expression in mouse liver.Science advances · 2026Article
- Divergent signaling profiles in mTOR gain-of-function Smith-Kingsmore syndrome (SKS) and TSC2 deficiency.bioRxiv : the preprint server for biology · 2026Article
- Core Circadian Protein BMAL1: Implication for Nervous System Functioning and Its Diseases.Brain sciences · 2025Review
- Autism Spectrum Disorder: The Cerebellum, Genes, and Pathways.Neurology international · 2025Review
- Validation of the self-report quantified Tuberous Sclerosis Complex-Associated Neuropsyciatric Disorders Checklist (TAND-SQ).Orphanet journal of rare diseases · 2025Article
- Circadian system and aging: where both times interact.Frontiers in aging · 2025Review
- Do metabolic deficits contribute to sleep disruption in monogenic intellectual disability syndromes?Trends in neurosciences · 2024Review
- Circadian regulation of macromolecular complex turnover and proteome renewal.The EMBO journal · 2024Article
- Coordination between circadian neural circuit and intracellular molecular clock ensures rhythmic activation of adult neural stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Targeting the circadian modulation: novel therapeutic approaches in the management of ASD.Frontiers in psychiatry · 2024Review
- Synaptic BMAL1 phosphorylation controls circadian hippocampal plasticity.Science advances · 2023Article
- Increased degradation of FMRP contributes to neuronal hyperexcitability in tuberous sclerosis complex.Cell reports · 2023Article
- The Case for the Target of Rapamycin Pathway as a Candidate Circadian Oscillator.International journal of molecular sciences · 2023Review
- mTORC1 activity negatively regulates human hair follicle growth and pigmentation.EMBO reports · 2023Article
- Loss of sleep when it is needed most - Consequences of persistent developmental sleep disruption: A scoping review of rodent models.Neurobiology of sleep and circadian rhythms · 2023Article
- Circadian disruption: from mouse models to molecular mechanisms and cancer therapeutic targets.Cancer metastasis reviews · 2023Review
- Control of circadian rhythm on cortical excitability and synaptic plasticity.Frontiers in neural circuits · 2023Review
- Dominant constraints on the evolution of rhythmic gene expression.Computational and structural biotechnology journal · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder characterized by mutations in either the TSC1 or TSC2 genes, whose products form a critical inhibitor of the mechanistic target of rapamycin (mTOR). Loss of TSC1/2 gene function renders an mTOR-overactivated state. Clinically, TSC manifests with epilepsy, intellectual disability, autism, and sleep dysfunction. Here, we report that mouse models of TSC have abnormal circadian rhythms. We show that mTOR regulates the proteostasis of the core clock protein BMAL1, affecting its translation, degradation, and subcellular localization. This results in elevated levels of BMAL1 and a dysfunctional clock that displays abnormal timekeeping under constant conditions and exaggerated responses to phase resetting. Genetically lowering the dose of BMAL1 rescues circadian behavioral phenotypes in TSC mouse models. These findings indicate that BMAL1 deregulation is a feature of the mTOR-activated state and suggest a molecular mechanism for mitigating circadian phenotypes in a neurodevelopmental disorder.
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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.