ArticlePloS one2021
Decreased glucocerebrosidase activity and substrate accumulation of glycosphingolipids in a novel GBA1 D409V knock-in mouse model.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- Reactive astrocytes mediate toxicity in iPSC derived dopaminergic neurons.NPJ Parkinson's disease · 2026Article
- Sphingolipidoses: expanding the spectrum of α-synucleinopathies.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Unraveling the intersection of aging and Parkinson's disease: a collaborative roadmap for advancing research models.NPJ Parkinson's disease · 2026Review
- Long-term oral glucocerebrosidase activator reduces soluble α-synuclein oligomer accumulation in Parkinsonian LRRK2 mutant mouse brain.NPJ Parkinson's disease · 2025Article
- Inhibition or genetic reduction of ASAH1/acid ceramidase restore α-synuclein clearance in mutant GBA1 dopamine neurons from Parkinson's patients.Human molecular genetics · 2025Article
- Systemically delivered lipid nanoparticle-mRNA encoding lysosomal acid β-glucosidase restores the enzyme deficiency in a murine Gaucher disease model.Gene therapy · 2025Article
- FLT201, a novel liver-directed AAV gene therapy candidate for Gaucher disease type 1.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Lysosomal glucocerebrosidase is needed for ciliary Hedgehog signaling: A convergent pathway contributing to Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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- Sidransky Syndrome-International journal of molecular sciences · 2025Review
- Multiomics analysis provides insights into musk secretion in muskrat and musk deer.GigaScience · 2025Article
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- Preclinical insights into gamma-tACS: foundations for clinical translation in neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- Neither alpha-synuclein fibril strain nor host murine genotype influences seeding efficacy.NPJ Parkinson's disease · 2024Article
- Targeting neuronal lysosomal dysfunction caused by β-glucocerebrosidase deficiency with an enzyme-based brain shuttle construct.Nature communications · 2023Article
- Neuronopathic GBA1L444P Mutation Accelerates Glucosylsphingosine Levels and Formation of Hippocampal Alpha-Synuclein Inclusions.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Review
- Aging, Parkinson's Disease, and Models: What Are the Challenges?Aging biology · 2023Article
- Lysosomal Pathogenesis of Parkinson's Disease: Insights From LRRK2 and GBA1 Rodent Models.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Live cellFrontiers in cellular neuroscience · 2023Article
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Authors and funding
20 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple mutations have been described in the human GBA1 gene, which encodes the lysosomal enzyme beta-glucocerebrosidase (GCase) that degrades glucosylceramide and is pivotal in glycosphingolipid substrate metabolism. Depletion of GCase, typically by homozygous mutations in GBA1, is linked to the lysosomal storage disorder Gaucher's disease (GD) and distinct or heterozygous mutations in GBA1 are associated with increased Parkinson's disease (PD) risk. While numerous genes have been linked to heritable PD, GBA1 mutations in aggregate are the single greatest risk factor for development of idiopathic PD. The importance of GCase in PD necessitates preclinical models in which to study GCase-related mechanisms and novel therapeutic approaches, as well as to elucidate the molecular mechanisms leading to enhanced PD risk in GBA1 mutation carriers. The aim of this study was to develop and characterize a novel GBA1 mouse model and to facilitate wide accessibility of the model with phenotypic data. Herein we describe the results of molecular, biochemical, histological, and behavioral phenotyping analyses in a GBA1 D409V knock-in (KI) mouse. This mouse model exhibited significantly decreased GCase activity in liver and brain, with substantial increases in glycosphingolipid substrates in the liver. While no changes in the number of dopamine neurons in the substantia nigra were noted, subtle changes in striatal neurotransmitters were observed in GBA1 D409V KI mice. Alpha-synuclein pathology and inflammation were not observed in the nigrostriatal system of this model. In summary, the GBA1 D409V KI mouse model provides an ideal model for studies aimed at pharmacodynamic assessments of potential therapies aiming to restore GCase.
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