ArticleScientific reports2016
Parkinson disease-linked GBA mutation effects reversed by molecular chaperones in human cell and fly models.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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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.
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Who cites it
87 citing papers in PubMed, 159 citations in OpenAlex.
- Clinical course and biomarkers in patients with type 1 Gaucher disease and Parkinson's disease: A retrospective cohort study.Molecular genetics and metabolism reports · 2026Article
- Glucocerebrosidase dysfunction in GBA1 carriers: insights from blood and macrophage analyses.Molecular biology reports · 2026Article
- Shared and distinct lipid profiles in amygdala from sporadic and GBA-associated Parkinson's diseases.NPJ Parkinson's disease · 2026Article
- Two lysosomal genes ATP13A2 and GBA1 interact to drive neurodegeneration.Molecular neurodegeneration · 2026Article
- The modifying effect of mutant LRRK2 on mutant GBA1-associated Parkinson disease.Human molecular genetics · 2025Article
- Developing nanobodies as allosteric molecular chaperones of glucocerebrosidase function.Nature communications · 2025Article
- Allosteric Modulation of GCase Enhances Lysosomal Activity and Reduces ER Stress in GCase-Related Disorders.International journal of molecular sciences · 2025Article
- Sidransky Syndrome-International journal of molecular sciences · 2025Review
- Electric-field induced sleep promotion and lifespan extension in Gaucher's disease model flies.Biochemistry and biophysics reports · 2025Article
- Current opinion on pluripotent stem cell technology in Gaucher's disease: challenges and future prospects.Cytotechnology · 2025Review
- Mass spectrometry-based proteomics for biomarker discovery in theNeuroprotection (Chichester, England) · 2024Review
- Clinical, mechanistic, biomarker, and therapeutic advances in GBA1-associated Parkinson's disease.Translational neurodegeneration · 2024Review
- Variant-specific effects of GBA1 mutations on dopaminergic neuron proteostasis.Journal of neurochemistry · 2024Article
- An Inducible Luminescent System to Explore Parkinson's Disease-Associated Genes.International journal of molecular sciences · 2024Article
- Review
- 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 consequences ofNeural regeneration research · 2024Article
- Twelve Years of Drug Prioritization to Help Accelerate Disease Modification Trials in Parkinson's Disease: The International Linked Clinical Trials Initiative.Journal of Parkinson's disease · 2024Review
- Whole Transcriptome Analysis of Substantia Nigra in Mice with MPTP-Induced Parkinsonism Bearing Defective Glucocerebrosidase Activity.International journal of molecular sciences · 2023Article
- The Management of Parkinson's Disease: An Overview of the Current Advancements in Drug Delivery Systems.Pharmaceutics · 2023Review
27 more citing papers are in PubMed but not listed here.
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6 authors at 2 institutions in 1 country.
Funding
Abstract
GBA gene mutations are the greatest cause of Parkinson disease (PD). GBA encodes the lysosomal enzyme glucocerebrosidase (GCase) but the mechanisms by which loss of GCase contributes to PD remain unclear. Inhibition of autophagy and the generation of endoplasmic reticulum (ER) stress are both implicated. Mutant GCase can unfold in the ER and be degraded via the unfolded protein response, activating ER stress and reducing lysosomal GCase. Small molecule chaperones that cross the blood brain barrier help mutant GCase refold and traffic correctly to lysosomes are putative treatments for PD. We treated fibroblast cells from PD patients with heterozygous GBA mutations and Drosophila expressing human wild-type, N370S and L444P GBA with the molecular chaperones ambroxol and isofagomine. Both chaperones increased GCase levels and activity, but also GBA mRNA, in control and mutant GBA fibroblasts. Expression of mutated GBA in Drosophila resulted in dopaminergic neuronal loss, a progressive locomotor defect, abnormal aggregates in the ER and increased levels of the ER stress reporter Xbp1-EGFP. Treatment with both chaperones lowered ER stress and prevented the loss of motor function, providing proof of principle that small molecule chaperones can reverse mutant GBA-mediated ER stress in vivo and might prove effective for treating PD.
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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.