ArticleHuman molecular genetics2022
Lysosomal ceramides regulate cathepsin B-mediated processing of saposin C and glucocerebrosidase activity.
Article in Human molecular genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 35 citations in OpenAlex.
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- Exercise, exerkines, and muscle-brain crosstalk in Parkinson's disease.Neuroprotection (Chichester, England) · 2026Review
- Pathogenic variants in BORCS5 cause a spectrum of neurodevelopmental and neurodegenerative disorders with lysosomal dysfunction.The Journal of clinical investigation · 2026Article
- Prosaposin in CNS health and disease, metabolic stress and exercise adaptation.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Prosaposin Is Cleaved Into Saposins by Multiple Cathepsins in a Progranulin-Regulated Fashion.Journal of neurochemistry · 2026Article
- Abnormal Splicing ofBiomedicines · 2025Article
- TMEM175, SCARB2 and CTSB associations with Parkinson's disease risk across populations.NPJ Parkinson's disease · 2025Article
- Enzyme Activity-Based Genome-wide Screening for Modifiers of Lysosomal Glucocerebrosidase Uncovers Candidate Risk Factors for Parkinson's Disease.ACS central science · 2025Article
- Recombinant cathepsins B and L promote α-synuclein clearance and restore lysosomal function in human and murine models with α-synuclein pathology.Molecular neurodegeneration · 2025Article
- Review
- Calcium modulating ligand confers risk for Parkinson's disease and impacts lysosomes.Annals of clinical and translational neurology · 2025Article
- Prioritizing Parkinson's disease risk genes in genome-wide association loci.NPJ Parkinson's disease · 2025Article
- Multi-omics analysis of the potential association between metabolic features of hypothyroidism in the first half of pregnancy and Th17/Treg balance.Frontiers in immunology · 2025Article
- The Parkinson's disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons.Molecular neurodegeneration · 2024Article
- A novel homozygousThe Journal of international medical research · 2024Article
- Late-onset Krabbe disease presenting as spastic paraplegia - implications of GCase and CTSB/D.Annals of clinical and translational neurology · 2024Article
- Cell biology of Parkinson's disease: Mechanisms of synaptic, lysosomal, and mitochondrial dysfunction.Current opinion in neurobiology · 2024Review
- The Parkinson's disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons.Research square · 2024Article
- Inhibition of cysteine protease cathepsin L increases the level and activity of lysosomal glucocerebrosidase.JCI insight · 2024Article
- Cathepsins and Parkinson's disease: insights from Mendelian randomization analyses.Frontiers in aging neuroscience · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Variants in multiple lysosomal enzymes increase Parkinson's disease (PD) risk, including the genes encoding glucocerebrosidase (GCase), acid sphingomyelinase (ASMase) and galactosylceramidase. Each of these enzymes generates ceramide by hydrolysis of sphingolipids in lysosomes, but the role of this common pathway in PD pathogenesis has not yet been explored. Variations in GBA1, the gene encoding GCase, are the most common genetic risk factor for PD. The lysosomal enzyme cathepsin B has recently been implicated as an important genetic modifier of disease penetrance in individuals harboring GBA1 variants, suggesting a mechanistic link between these enzymes. Here, we found that ceramide activates cathepsin B, and identified a novel role for cathepsin B in mediating prosaposin cleavage to form saposin C, the lysosomal coactivator of GCase. Interestingly, this pathway was disrupted in Parkin-linked PD models, and upon treatment with inhibitor of ASMase which resulted in decreased ceramide production. Conversely, increasing ceramide production by inhibiting acid ceramidase activity was sufficient to upregulate cathepsin B- and saposin C-mediated activation of GCase. These results highlight a mechanistic link between ceramide and cathepsin B in regulating GCase activity and suggest that targeting lysosomal ceramide or cathepsin B represents an important therapeutic strategy for activating GCase in PD and related disorders.
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.