ArticlePLoS genetics2016
Glucocerebrosidase Deficiency in Drosophila Results in α-Synuclein-Independent Protein Aggregation and Neurodegeneration.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 307 citations in OpenAlex.
- Two lysosomal genes ATP13A2 and GBA1 interact to drive neurodegeneration.Molecular neurodegeneration · 2026Article
- Constraint-based modelling of metabolic dysregulation in Gaucher disease: mitochondrial dysfunction and disrupted cholesterol homeostasis.Orphanet journal of rare diseases · 2026Article
- Functional profiling and visualization of the sphingolipid metabolic network in vivo.EMBO reports · 2025Article
- The modifying effect of mutant LRRK2 on mutant GBA1-associated Parkinson disease.Human molecular genetics · 2025Article
- Glia phagocytose neuronal sphingolipids to infiltrate developing synapses.bioRxiv : the preprint server for biology · 2025Article
- Electric-field induced sleep promotion and lifespan extension in Gaucher's disease model flies.Biochemistry and biophysics reports · 2025Article
- Unifying biology of neurodegeneration in lysosomal storage diseases.Journal of inherited metabolic disease · 2025Review
- Glucocerebrosidase deficiency leads to neuropathology via cellular immune activation.PLoS genetics · 2024Article
- Does glial lipid dysregulation alter sleep in Alzheimer's and Parkinson's disease?Trends in molecular medicine · 2024Review
- Functional Analysis of HumanCells · 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
- Biochemical Fractionation of Human α-Synuclein in aInternational journal of molecular sciences · 2024Article
- Glucocerebrosidase deficiency leads to neuropathology via cellular immune activation.bioRxiv : the preprint server for biology · 2023Article
- Autophagic dysfunction and gut microbiota dysbiosis cause chronic immune activation in a Drosophila model of Gaucher disease.PLoS genetics · 2023Article
- Animal Models for the Study of Gaucher Disease.International journal of molecular sciences · 2023Review
- Functional screening of lysosomal storage disorder genes identifies modifiers of alpha-synuclein neurotoxicity.PLoS genetics · 2023Article
- ATP13A2 Gene Silencing in Drosophila Affects Autophagic Degradation of A53T Mutant α-Synuclein.International journal of molecular sciences · 2023Article
- Sphingolipids in neurodegenerative diseases.Frontiers in neuroscience · 2023Review
- Review
- Glial control of sphingolipid levels sculpts diurnal remodeling in a circadian circuit.Neuron · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in the glucosidase, beta, acid (GBA1) gene cause Gaucher's disease, and are the most common genetic risk factor for Parkinson's disease (PD) and dementia with Lewy bodies (DLB) excluding variants of low penetrance. Because α-synuclein-containing neuronal aggregates are a defining feature of PD and DLB, it is widely believed that mutations in GBA1 act by enhancing α-synuclein toxicity. To explore this hypothesis, we deleted the Drosophila GBA1 homolog, dGBA1b, and compared the phenotypes of dGBA1b mutants in the presence and absence of α-synuclein expression. Homozygous dGBA1b mutants exhibit shortened lifespan, locomotor and memory deficits, neurodegeneration, and dramatically increased accumulation of ubiquitinated protein aggregates that are normally degraded through an autophagic mechanism. Ectopic expression of human α-synuclein in dGBA1b mutants resulted in a mild enhancement of dopaminergic neuron loss and increased α-synuclein aggregation relative to controls. However, α-synuclein expression did not substantially enhance other dGBA1b mutant phenotypes. Our findings indicate that dGBA1b plays an important role in the metabolism of protein aggregates, but that the deleterious consequences of mutations in dGBA1b are largely independent of α-synuclein. Future work with dGBA1b mutants should reveal the mechanism by which mutations in dGBA1b lead to accumulation of protein aggregates, and the potential influence of this protein aggregation on neuronal integrity.
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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.