ArticleThe American journal of pathology2009
Protective role of endogenous gangliosides for lysosomal pathology in a cellular model of synucleinopathies.
Article in The American journal of pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 63 citations in OpenAlex.
- GM1 ganglioside in Parkinson's disease: Pilot study of effects on dopamine transporter binding.Journal of the neurological sciences · 2015Trial
- A randomized, controlled, delayed start trial of GM1 ganglioside in treated Parkinson's disease patients.Journal of the neurological sciences · 2013Trial
- α2-3-sialylated glycosphingolipids in neuroinflammation, immunity, and programmed cell death: mechanistic evidence and context-dependent regulation: a comprehensive review.Frontiers in immunology · 2026Review
- Interactions Between Extracellular Vesicles and Autophagy in Neuroimmune Disorders.Neuroscience bulletin · 2024Review
- Gut microbiota metabolites: potential therapeutic targets for Alzheimer's disease?Frontiers in pharmacology · 2024Review
- Modulating glycosphingolipid metabolism and autophagy improves outcomes in pre-clinical models of myeloma bone disease.Nature communications · 2022Article
- A critical role for GM1 ganglioside in the pathophysiology and potential treatment of Parkinson's disease.Glycoconjugate journal · 2022Review
- The impact of the glycan headgroup on the nanoscopic segregation of gangliosides.Biophysical journal · 2021Article
- Genetics of synucleins in neurodegenerative diseases.Acta neuropathologica · 2021Review
- Therapeutic Potential of αS Evolvability for Neuropathic Gaucher Disease.Biomolecules · 2021Article
- Possible Role of Amyloidogenic Evolvability in Dementia with Lewy Bodies: Insights from Transgenic Mice Expressing P123H β-Synuclein.International journal of molecular sciences · 2020Review
- Gangliosides in the Brain: Physiology, Pathophysiology and Therapeutic Applications.Frontiers in neuroscience · 2020Review
- Role of Glucosylceramide in Lung Endothelial Cell Fate and Emphysema.American journal of respiratory and critical care medicine · 2019Article
- Preparation of Ganglioside GM1 by Supercritical COMolecules (Basel, Switzerland) · 2019Article
- GM1 Ganglioside Modifies α-Synuclein Toxicity and is Neuroprotective in a Rat α-Synuclein Model of Parkinson's Disease.Scientific reports · 2019Article
- The Role of Lipids in Parkinson's Disease.Cells · 2019Review
- Dysregulated Lipid Metabolism and Its Role in α-Synucleinopathy in Parkinson's Disease.Frontiers in neuroscience · 2019Review
- Glucocerebrosidase mRNA is Diminished in Brain of Lewy Body Diseases and Changes with Disease Progression in Blood.Aging and disease · 2018Article
- Chaperone-Mediated Autophagy after Traumatic Brain Injury.Journal of neurotrauma · 2015Article
- Gaucher-Associated Parkinsonism.Cellular and molecular neurobiology · 2015Review
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gangliosides may be involved in the pathogenesis of Parkinson's disease and related disorders, although the precise mechanisms governing this involvement remain unknown. In this study, we determined whether changes in endogenous ganglioside levels affect lysosomal pathology in a cellular model of synucleinopathy. For this purpose, dementia with Lewy body-linked P123H beta-synuclein (beta-syn) neuroblastoma cells transfected with alpha-synuclein were used as a model system because these cells were characterized as having extensive formation of lysosomal inclusions bodies. Treatment of these cells with D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), an inhibitor of glycosyl ceramide synthase, resulted in various features of lysosomal pathology, including compromised lysosomal activity, enhanced lysosomal membrane permeabilization, and increased cytotoxicity. Consistent with these findings, expression levels of lysosomal membrane proteins, ATP13A2 and LAMP-2, were significantly decreased, and electron microscopy demonstrated alterations in the lysosomal membrane structures. Furthermore, the accumulation of both P123H beta-syn and alpha-synuclein proteins was significant in PDMP-treated cells because of the suppressive effect of PDMP on the autophagy pathway. Finally, the detrimental effects of PDMP on lysosomal pathology were significantly ameliorated by the addition of gangliosides to the cultured cells. These data suggest that endogenous gangliosides may play protective roles against the lysosomal pathology of synucleinopathies.
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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.