ArticleHuman molecular genetics2015
Glucocerebrosidase 1 deficient Danio rerio mirror key pathological aspects of human Gaucher disease and provide evidence of early microglial activation preceding alpha-synuclein-independent neuronal cell death.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.
- Patient centered guidelines for the laboratory diagnosis of Gaucher disease type 1.Orphanet journal of rare diseases · 2022Guideline
- Two lysosomal genes ATP13A2 and GBA1 interact to drive neurodegeneration.Molecular neurodegeneration · 2026Article
- Article
- Underlying Mechanisms of GBA1 in Parkinson's Disease and Dementia with Lewy Bodies: Narrative Review.Genes · 2025Review
- Telomerase Depletion Accelerates Ageing of the Zebrafish Brain.Aging cell · 2025Article
- Metabolic reprogramming and altered ATP content impair neuroprotective functions of microglia in β-glucocerebrosidase deficiency models.Journal of neuroinflammation · 2025Article
- A zebrafish model of acmsd deficiency does not support a prominent role for ACMSD in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- C9ORF72 Deficiency Results in Neurodegeneration in the Zebrafish Retina.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Lysosomal storage, impaired autophagy and innate immunity in Gaucher and Parkinson's diseases: insights for drug discovery.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- High NaCl Concentrations in Water Are Associated with Developmental Abnormalities and Altered Gene Expression in Zebrafish.International journal of molecular sciences · 2024Article
- Inhibition of cysteine protease cathepsin L increases the level and activity of lysosomal glucocerebrosidase.JCI insight · 2024Article
- Review
- Animal Models for the Study of Gaucher Disease.International journal of molecular sciences · 2023Review
- Proteomic analysis unveils Gb3-independent alterations and mitochondrial dysfunction in a glaJournal of translational medicine · 2023Article
- A zebrafish model of combined saposin deficiency identifies acid sphingomyelinase as a potential therapeutic target.Disease models & mechanisms · 2023Article
- Unexpected phenotypic and molecular changes of combined glucocerebrosidase and acid sphingomyelinase deficiency.Disease models & mechanisms · 2023Article
- Zebra-Sphinx: Modeling Sphingolipidoses in Zebrafish.International journal of molecular sciences · 2023Review
- Gaucher disease protects against tuberculosis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Advances in Zebrafish as a Comprehensive Model of Mental Disorders.Depression and anxiety · 2023Review
9 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 9 institutions in 4 countries.
Funding
Abstract
Autosomal recessively inherited glucocerebrosidase 1 (GBA1) mutations cause the lysosomal storage disorder Gaucher's disease (GD). Heterozygous GBA1 mutations (GBA1(+/-)) are the most common risk factor for Parkinson's disease (PD). Previous studies typically focused on the interaction between the reduction of glucocerebrosidase (enzymatic) activity in GBA1(+/-) carriers and alpha-synuclein-mediated neurotoxicity. However, it is unclear whether other mechanisms also contribute to the increased risk of PD in GBA1(+/-) carriers. The zebrafish genome does not contain alpha-synuclein (SNCA), thus providing a unique opportunity to study pathogenic mechanisms unrelated to alpha-synuclein toxicity. Here we describe a mutant zebrafish line created by TALEN genome editing carrying a 23 bp deletion in gba1 (gba1(c.1276_1298del)), the zebrafish orthologue of human GBA1. Marked sphingolipid accumulation was already detected at 5 days post-fertilization with accompanying microglial activation and early, sustained up-regulation of miR-155, a master regulator of inflammation. gba1(c.1276_1298del) mutant zebrafish developed a rapidly worsening phenotype from 8 weeks onwards with striking reduction in motor activity by 12 weeks. Histopathologically, we observed marked Gaucher cell invasion of the brain and other organs. Dopaminergic neuronal cell count was normal through development but reduced by >30% at 12 weeks in the presence of ubiquitin-positive, intra-neuronal inclusions. This gba1(c.1276_1298del) zebrafish line is the first viable vertebrate model sharing key pathological features of GD in both neuronal and non-neuronal tissue. Our study also provides evidence for early microglial activation prior to alpha-synuclein-independent neuronal cell death in GBA1 deficiency and suggests upregulation of miR-155 as a common denominator across different neurodegenerative disorders.
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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.