ArticleCells2021
L-Arginine Ameliorates Defective Autophagy in GM2 Gangliosidoses by mTOR Modulation.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 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.
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Who cites it
5 citing papers in PubMed, 9 citations in OpenAlex.
- Modeling Tay-Sachs Disease in Astrocyte-like Cells Reveals Significant Changes in the Transcriptomic Profile.International journal of molecular sciences · 2026Article
- Review
- Genetic mutation and immune infiltration in embryonal tumor with multilayered rosettes.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024Article
- Autophagy: Are Amino Acid Signals Dependent on the mTORC1 Pathway or Independent?Current issues in molecular biology · 2024Review
- Review
Corrections and comments
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Authors and funding
12 authors at 9 institutions in 2 countries.
Funding
Abstract
aimsTay-Sachs and Sandhoff diseases (GM2 gangliosidosis) are autosomal recessive disorders of lysosomal function that cause progressive neurodegeneration in infants and young children. Impaired hydrolysis catalysed by β-hexosaminidase A (HexA) leads to the accumulation of GM2 ganglioside in neuronal lysosomes. Despite the storage phenotype, the role of autophagy and its regulation by mTOR has yet to be explored in the neuropathogenesis. Accordingly, we investigated the effects on autophagy and lysosomal integrity using skin fibroblasts obtained from patients with Tay-Sachs and Sandhoff diseases.
resultsPathological autophagosomes with impaired autophagic flux, an abnormality confirmed by electron microscopy and biochemical studies revealing the accelerated release of mature cathepsins and HexA into the cytosol, indicating increased lysosomal permeability. GM2 fibroblasts showed diminished mTOR signalling with reduced basal mTOR activity. Accordingly, provision of a positive nutrient signal by L-arginine supplementation partially restored mTOR activity and ameliorated the cytopathological abnormalities. INNOVATION: Our data provide a novel molecular mechanism underlying GM2 gangliosidosis. Impaired autophagy caused by insufficient lysosomal function might represent a new therapeutic target for these diseases.
conclusionsWe contend that the expression of autophagy/lysosome/mTOR-associated molecules may prove useful peripheral biomarkers for facile monitoring of treatment of GM2 gangliosidosis and neurodegenerative disorders that affect the lysosomal function and disrupt autophagy.
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Registered trials
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