ArticlePloS one2018
Analysis of age-related changes in psychosine metabolism in the human brain.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
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Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- GALC variants affect galactosylceramidase enzymatic activity and risk of Parkinson's disease.Brain : a journal of neurology · 2023Pooled it
- Emerging links between pediatric lysosomal storage diseases and adult parkinsonism.Movement disorders : official journal of the Movement Disorder Society · 2019Pooled it
- Shared and Sex-Specific Genetic Risk for Parkinson's Disease Risk Across European Populations.medRxiv : the preprint server for health sciences · 2026Article
- Dysfunctional digestive tract highlights the metabolic hallmarks of nanoplastic-exacerbated Parkinson's pathology.NPJ Parkinson's disease · 2025Article
- Deficiency of galactosyl-ceramidase in adult oligodendrocytes worsens disease severity during chronic experimental allergic encephalomyelitis.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Lysosomal dysfunction in α-synuclein pathology: molecular mechanisms and therapeutic strategies.Cellular and molecular life sciences : CMLS · 2024Review
- Galactosylceramidase deficiency and pathological abnormalities in cerebral white matter of Krabbe disease.Neurobiology of disease · 2022Article
- Prion-like α-synuclein pathology in the brain of infants with Krabbe disease.Brain : a journal of neurology · 2022Article
- Fatty acid-binding protein 7 triggers α-synuclein oligomerization in glial cells and oligodendrocytes associated with oxidative stress.Acta pharmacologica Sinica · 2022Article
- Glycosphingolipid metabolism and its role in ageing and Parkinson's disease.Glycoconjugate journal · 2022Review
- Insights into Lewy body disease from rare neurometabolic disorders.Journal of neural transmission (Vienna, Austria : 1996) · 2021Review
- Review
- Sphingolipids as Regulators of Neuro-Inflammation and NADPH Oxidase 2.Neuromolecular medicine · 2021Review
- Krabbe Disease: Prospects of Finding a Cure Using AAV Gene Therapy.Frontiers in medicine · 2021Review
- Deregulation of signalling in genetic conditions affecting the lysosomal metabolism of cholesterol and galactosyl-sphingolipids.Neurobiology of disease · 2020Review
- Lysosomal Ceramide Metabolism Disorders: Implications in Parkinson's Disease.Journal of clinical medicine · 2020Review
- AAV-Mediated GALC Gene Therapy Rescues Alpha-Synucleinopathy in the Spinal Cord of a Leukodystrophic Lysosomal Storage Disease Mouse Model.Frontiers in cellular neuroscience · 2020Article
- Reduced sphingolipid hydrolase activities, substrate accumulation and ganglioside decline in Parkinson's disease.Molecular neurodegeneration · 2019Article
- α-Synuclein interacts directly but reversibly with psychosine: implications for α-synucleinopathies.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
α-Synuclein aggregation has been linked to Gaucher's disease (GD) and Krabbe's disease (KD), lysosomal conditions affecting glycosphingolipid metabolism. α-Synuclein pathology has been directly attributed to the dysregulation of glycosphingolipids in both conditions, specifically to increased galactosylsphingosine (psychosine) content in the context of KD. Furthermore, the gene (GALC) coding for the psychosine degrading enzyme galactosylceramidase (GALC), has recently been identified as a risk loci for Parkinson's disease. However, it is unknown if changes in psychosine metabolism and GALC activity in the context of the aging human brain correlate with Parkinson's disease. We investigated psychosine accumulation and GALC activity in the aging brain using fresh frozen post-mortem tissue from Parkinson's (PD, n = 10), Alzheimer's (AD, n = 10), and healthy control patients (n = 9), along with tissue from neuropsychiatric patients (schizophrenia, bipolar disorder and depression, n = 15 each). An expanded mutational analysis of PD (n = 20), AD (n = 10), and healthy controls (n = 30) examined if PD was correlated with carriers for severe GALC mutations. Psychosine content within the cerebral cortex of PD patients was elevated above control patients. Within all patients, psychosine displayed a significant (p<0.05) and robust regional distribution in the brain with higher levels in the white matter and substantia nigra. A mutational analysis revealed an increase in the incidence of severe GALC mutations within the PD patient population compared to the cohorts of Alzheimer's patients and healthy controls tested. In addition to α-synuclein pathology identified in the KD brain, control patients identified as GALC mutational carriers or possessing a GALC pathogenic variant had evidence of α-synuclein pathology, indicating a possible correlation between α-synuclein pathology and dysregulation of psychosine metabolism in the adult brain. Carrier status for GALC mutations and prolonged exposure to increased psychosine could contribute to α-synuclein pathology, supporting psychosine metabolism by galactosylceramidase as a risk factor for Parkinson's disease.
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