ArticleHuman molecular genetics2016
Glucocerebrosidase modulates cognitive and motor activities in murine models of Parkinson's disease.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- Underlying Mechanisms of GBA1 in Parkinson's Disease and Dementia with Lewy Bodies: Narrative Review.Genes · 2025Review
- A pathogenic alpha synuclein variant exacerbates disease progression in a neuron-specific Gba-KO mouse.Neurobiology of disease · 2025Article
- Synaptic and cognitive impairment associated with L444P heterozygous glucocerebrosidase mutation.Brain : a journal of neurology · 2025Article
- Recent developments in gene therapy for Parkinson's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Article
- Non-Categorical Analyses Identify Rotenone-Induced 'Parkinsonian' Rats Benefiting from Nano-Emulsified Punicic Acid (Nano-PSO) in a Phenotypically Diverse Population: Implications for Translational Neurodegenerative Therapies.International journal of molecular sciences · 2024Article
- Single-domain antibody-based protein degrader for synucleinopathies.Molecular neurodegeneration · 2024Article
- Single-Domain Antibody-Based Protein Degrader for Synucleinopathies.bioRxiv : the preprint server for biology · 2024Article
- iPSC-derived neural precursor cells engineeringMolecular therapy. Methods & clinical development · 2023Article
- Review
- A Mouse Model to Test Novel Therapeutics for Parkinson's Disease: an Update on the Thy1-aSyn ("line 61") Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- How Well Do Rodent Models of Parkinson's Disease Recapitulate Early Non-Motor Phenotypes? A Systematic Review.Biomedicines · 2022Review
- Calmodulin Binding Domains in Critical Risk Proteins Involved in Neurodegeneration.Current issues in molecular biology · 2022Article
- Alpha-Synuclein Targeting Therapeutics for Parkinson's Disease and Related Synucleinopathies.Frontiers in neurology · 2022Review
- Wild-type GBA1 increases the α-synuclein tetramer-monomer ratio, reduces lipid-rich aggregates, and attenuates motor and cognitive deficits in mice.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Genotype-driven therapeutic developments in Parkinson's disease.Molecular medicine (Cambridge, Mass.) · 2021Review
- Review
- Review
- Glucocerebrosidase Activity Modulates Neuronal Susceptibility to Pathological α-Synuclein Insult.Neuron · 2020Article
- GBA1 mutations: Prospects for exosomal biomarkers in α-synuclein pathologies.Molecular genetics and metabolism · 2020Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in GBA1, the gene encoding glucocerebrosidase, are associated with an enhanced risk of developing synucleinopathies such as Parkinson's disease (PD) and dementia with Lewy bodies. A higher prevalence and increased severity of motor and non-motor symptoms is observed in PD patients harboring mutant GBA1 alleles, suggesting a link between the gene or gene product and disease development. Interestingly, PD patients without mutations in GBA1 also exhibit lower levels of glucocerebrosidase activity in the central nervous system (CNS), implicating this lysosomal enzyme in disease pathogenesis. Here, we investigated whether modulation of glucocerebrosidase activity in murine models of synucleinopathy (expressing wild type Gba1) affected α-synuclein accumulation and behavioral phenotypes. Partial inhibition of glucocerebrosidase activity in PrP-A53T-SNCA mice using the covalent inhibitor conduritol-B-epoxide induced a profound increase in soluble α-synuclein in the CNS and exacerbated cognitive and motor deficits. Conversely, augmenting glucocerebrosidase activity in the Thy1-SNCA mouse model of PD delayed the progression of synucleinopathy. Adeno-associated virus-mediated expression of glucocerebrosidase in the Thy1-SNCA mouse striatum led to decrease in the levels of the proteinase K-resistant fraction of α-synuclein, amelioration of behavioral aberrations and protection from loss of striatal dopaminergic markers. These data indicate that increasing glucocerebrosidase activity can influence α-synuclein homeostasis, thereby reducing the progression of synucleinopathies. This study provides robust in vivo evidence that augmentation of CNS glucocerebrosidase activity is a potential therapeutic strategy for PD, regardless of the mutation status of GBA1.
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Registered trials
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