ArticleMolecular biology of the cell2013
Activation of serum/glucocorticoid-induced kinase 1 (SGK1) underlies increased glycogen levels, mTOR activation, and autophagy defects in Lafora disease.
Article in Molecular biology of the cell, 2013. 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 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- An astrocytic cellular model of Lafora disease to study polyglucosan accumulation and inflammation.Disease models & mechanisms · 2026Article
- Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain.Experimental neurology · 2024Review
- The role of SGK1 in neurologic diseases: A friend or foe?IBRO neuroscience reports · 2024Review
- Neuromuscular junction dysfunction in Lafora disease.Disease models & mechanisms · 2024Article
- Lafora progressive myoclonus epilepsy: Disease mechanism and therapeutic attempts.Journal of biosciences · 2024Review
- Glycogen overload transforms the liver.Acta biochimica et biophysica Sinica · 2022Article
- Age-Dependent Reduction in the Expression Levels of Genes Involved in Progressive Myoclonus Epilepsy Correlates with Increased Neuroinflammation and Seizure Susceptibility in Mouse Models.Molecular neurobiology · 2022Article
- SGK1, autophagy and cancer: an overview.Molecular biology reports · 2022Review
- Trehalose Ameliorates Seizure Susceptibility in Lafora Disease Mouse Models by Suppressing Neuroinflammation and Endoplasmic Reticulum Stress.Molecular neurobiology · 2021Article
- Glycogen: the missing link in neuronal autophagy?Autophagy · 2020Review
- SGK1 in Human Cancer: Emerging Roles and Mechanisms.Frontiers in oncology · 2020Review
- PLPP/CIN-mediated NEDD4-2 S448 dephosphorylation regulates neuronal excitability via GluA1 ubiquitination.Cell death & disease · 2019Article
- DominantAnnals of clinical and translational neurology · 2019Article
- Biomedical Implications of Autophagy in Macromolecule Storage Disorders.Frontiers in cell and developmental biology · 2019Review
- Loss of fragile X protein FMRP impairs homeostatic synaptic downscaling through tumor suppressor p53 and ubiquitin E3 ligase Nedd4-2.Human molecular genetics · 2018Article
- Review
- Lafora disease: from genotype to phenotype.Journal of genetics · 2018Review
- Glycogen synthase protects neurons from cytotoxicity of mutant huntingtin by enhancing the autophagy flux.Cell death & disease · 2018Article
- SGK1 inhibition induces autophagy-dependent apoptosis via the mTOR-Foxo3a pathway.British journal of cancer · 2017Article
- Loss of malin, but not laforin, results in compromised autophagic flux and proteasomal dysfunction in cells exposed to heat shock.Cell stress & chaperones · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lafora disease (LD), a fatal genetic form of myoclonic epilepsy, is characterized by abnormally high levels of cellular glycogen and its accumulation as Lafora bodies in affected tissues. Therefore the two defective proteins in LD-laforin phosphatase and malin ubiquitin ligase-are believed to be involved in glycogen metabolism. We earlier demonstrated that laforin and malin negatively regulate cellular glucose uptake by preventing plasma membrane targeting of glucose transporters. We show here that loss of laforin results in activation of serum/glucocorticoid-induced kinase 1 (SGK1) in cellular and animals models and that inhibition of SGK1 in laforin-deficient cells reduces the level of plasma membrane-bound glucose transporter, glucose uptake, and the consequent glycogen accumulation. We also provide evidence to suggest that mammalian target of rapamycin (mTOR) activates SGK1 kinase in laforin-deficient cells. The mTOR activation appears to be a glucose-dependent event, and overexpression of dominant-negative SGK1 suppresses mTOR activation, suggesting the existence of a feedforward loop between SGK1 and mTOR. Our findings indicate that inhibition of SGK1 activity could be an effective therapeutic approach to suppress glycogen accumulation, inhibit mTOR activity, and rescue autophagy defects in LD.
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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.