ArticleThe American journal of pathology2009
Increased activity and altered subcellular distribution of lysosomal enzymes determine neuronal vulnerability in Niemann-Pick type C1-deficient mice.
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 57 papers, 3 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 3 syntheses or guidelines pooled it, 88 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Guideline
- Lack of cathepsin B increases severity in Niemann-Pick disease, type C1 mice.Neuroscience letters · 2026Article
- Discovery of Autophagy Modulators that Increase I1061T NPC1 Expression and Promote Cholesterol Efflux in Niemann-Pick Type C Patient-Derived Fibroblasts.ACS chemical biology · 2026Article
- Microglial cathepsin B is necessary for neuronal efferocytosis in zebrafish and mice during brain development.Nature communications · 2026Article
- Review
- Distinct Cleavage Properties of Cathepsin B Compared to Cysteine Cathepsins Enable the Design and Validation of a Specific Substrate for Cathepsin B over a Broad pH Range.Biochemistry · 2023Article
- Cathepsin B Dipeptidyl Carboxypeptidase and Endopeptidase Activities Demonstrated across a Broad pH Range.Biochemistry · 2022Article
- Lysosomal peptidases-intriguing roles in cancer progression and neurodegeneration.FEBS open bio · 2022Review
- The CD22-IGF2R interaction is a therapeutic target for microglial lysosome dysfunction in Niemann-Pick type C.Science translational medicine · 2021Article
- Mimosine functionalized gold nanoparticles (Mimo-AuNPs) suppress β-amyloid aggregation and neuronal toxicity.Bioactive materials · 2021Article
- New Insights into the Role of Cysteine Cathepsins in Neuroinflammation.Biomolecules · 2021Review
- Implications of exosomes derived from cholesterol-accumulated astrocytes in Alzheimer's disease pathology.Disease models & mechanisms · 2021Article
- Selective Neutral pH Inhibitor of Cathepsin B Designed Based on Cleavage Preferences at Cytosolic and Lysosomal pH Conditions.ACS chemical biology · 2021Article
- Article
- Significance of cytosolic cathepsin D in Alzheimer's disease pathology: Protective cellular effects of PLGA nanoparticles against β-amyloid-toxicity.Neuropathology and applied neurobiology · 2020Article
- Fbxo2 mediates clearance of damaged lysosomes and modifies neurodegeneration in the Niemann-Pick C brain.JCI insight · 2020Article
- Single Cell Transcriptome Analysis of Niemann-Pick Disease, Type C1 Cerebella.International journal of molecular sciences · 2020Article
- The lysosome: A potential juncture between SARS-CoV-2 infectivity and Niemann-Pick disease type C, with therapeutic implications.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Niemann-Pick disease type C (NPC), caused by mutations in the Npc1 or Npc2 genes, is a progressive neurodegenerative disorder characterized by intracellular accumulation/redistribution of cholesterol in a number of tissues including the brain. This is accompanied by a severe loss of neurons in selected brain regions. In this study, we evaluated the role of lysosomal enzymes, cathepsins B and D, in determining neuronal vulnerability in NPC1-deficient (Npc1(-/-)) mouse brains. Our results showed that Npc1(-/-) mice exhibit an age-dependent degeneration of neurons in the cerebellum but not in the hippocampus. The cellular level/expression and activity of cathepsins B and D are increased more predominantly in the cerebellum than in the hippocampus of Npc1(-/-) mice. In addition, the cytosolic levels of cathepsins, cytochrome c, and Bax2 are higher in the cerebellum than in the hippocampus of Npc1(-/-) mice, suggesting a role for these enzymes in the degeneration of neurons. This suggestion is supported by our observation that degeneration of cultured cortical neurons treated with U18666A, which induces an NPC1-like phenotype at the cellular level, can be attenuated by inhibition of cathepsin B or D enzyme activity. These results suggest that the increased level/activity and altered subcellular distribution of cathepsins may be associated with the underlying cause of neuronal vulnerability in Npc1(-/-) brains. Therefore, their inhibitors may have therapeutic potential in attenuating NPC pathology.
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.