ArticleCell reports2018
Inhibition of Lysosome Membrane Recycling Causes Accumulation of Gangliosides that Contribute to Neurodegeneration.
Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 50 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Phase 2 Pharmacological Trial to Evaluate the Safety of Miglustat Administration in Subjects With Spastic Paraplegia 11 (TreatSPG11)
An Observational Study in Subjects With Spastic Paraplegia Type 11 Taking Trehalose
Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Pooled it
- Miglustat does not impact clinical progression in patients with spastic paraplegia type 11.Neurogenetics · 2025Trial
- Hereditary spastic paraplegia with thin corpus callosum and SPG11 mutation: A neuropathological evaluation.Neuropathology : official journal of the Japanese Society of Neuropathology · 2025Article
- Transcriptomic analysis reinforces the implication of spatacsin in neuroinflammation and neurodevelopment.Scientific reports · 2025Article
- Editorial: Translational research in hereditary spastic paraplegias: filling the diagnosis gap and therapeutic perspectives.Frontiers in neuroscience · 2025Article
- Unexpected complexity in the molecular diagnosis of spastic paraplegia 11.Molecular genetics & genomic medicine · 2024Article
- Article
- Pluripotent Stem Cells as a Preclinical Cellular Model for Studying Hereditary Spastic Paraplegias.International journal of molecular sciences · 2024Review
- Neuroinflammatory disease signatures in SPG11-related hereditary spastic paraplegia patients.Acta neuropathologica · 2024Article
- Diving deep: zebrafish models in motor neuron degeneration research.Frontiers in neuroscience · 2024Review
- Liver-X-receptor agonists rescue axonal degeneration in SPG11-deficient neurons via regulating cholesterol trafficking.Neurobiology of disease · 2023Article
- Spatacsin regulates directionality of lysosome trafficking by promoting the degradation of its partner AP5Z1.PLoS biology · 2023Article
- Lipid rafts and human diseases: why we need to target gangliosides.FEBS open bio · 2023Review
- Syringomyelia: A New Phenotype ofBrain & NeuroRehabilitation · 2023Article
- Autophagic lysosome reformation in health and disease.Autophagy · 2023Review
- Rescue of lysosomal function as therapeutic strategy for SPG15 hereditary spastic paraplegia.Brain : a journal of neurology · 2023Article
- Single Cerebral Organoid Mass Spectrometry of Cell-Specific Protein and Glycosphingolipid Traits.Analytical chemistry · 2023Article
- LYST deficiency impairs autophagic lysosome reformation in neurons and alters lysosome number and size.Cellular and molecular life sciences : CMLS · 2023Article
- Neuronal Ganglioside and Glycosphingolipid (GSL) Metabolism and Disease : Cascades of Secondary Metabolic Errors Can Generate Complex Pathologies (in LSDs).Advances in neurobiology · 2023Article
- In vitro substrate reduction, chaperone and immunomodulation treatments reduce heparan sulfate in mucolipidosis III human fibroblasts.Genetics and molecular biology · 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
20 authors at 9 institutions in 2 countries.
Funding
Abstract
Lysosome membrane recycling occurs at the end of the autophagic pathway and requires proteins that are mostly encoded by genes mutated in neurodegenerative diseases. However, its implication in neuronal death is still unclear. Here, we show that spatacsin, which is required for lysosome recycling and whose loss of function leads to hereditary spastic paraplegia 11 (SPG11), promotes clearance of gangliosides from lysosomes in mouse and human SPG11 models. We demonstrate that spatacsin acts downstream of clathrin and recruits dynamin to allow lysosome membrane recycling and clearance of gangliosides from lysosomes. Gangliosides contributed to the accumulation of autophagy markers in lysosomes and to neuronal death. In contrast, decreasing ganglioside synthesis prevented neurodegeneration and improved motor phenotype in a SPG11 zebrafish model. Our work reveals how inhibition of lysosome membrane recycling leads to the deleterious accumulation of gangliosides, linking lysosome recycling to neurodegeneration.
Indexed as
Identifiers
What OpenQuestion holds
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.