ArticleActa neuropathologica communications2018
D409H GBA1 mutation accelerates the progression of pathology in A53T α-synuclein transgenic mouse model.
Article in Acta neuropathologica communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Understanding the genetic imperfections of Lewy body dementia.Molecular neurodegeneration · 2026Review
- Knockout of Rab27b exacerbates neuropathology in alpha-synuclein mouse models.Acta neuropathologica communications · 2026Article
- Sphingolipidoses: expanding the spectrum of α-synucleinopathies.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Polymeric nanoparticle-mediated GBA1 gene therapy is neuroprotective in a preclinical model of Parkinson's disease.Drug delivery and translational research · 2026Article
- Stearoyl-CoA desaturase inhibition normalizes brain lipid saturation, α-synuclein homeostasis, and motor function in mutant Gba1-Parkinson mice.JCI insight · 2025Article
- Neurodegeneration models in Parkinson's disease: cellular and molecular paths to neuron death.Behavioral and brain functions : BBF · 2025Review
- Cryo-TEM structure of β-glucocerebrosidase in complex with its transporter LIMP-2.Nature communications · 2025Article
- A Comparative Biochemical and Pathological Evaluation of Brain Samples from Knock-In Murine Models of Gaucher Disease.International journal of molecular sciences · 2024Article
- The AAV-α-Synuclein Model of Parkinson's Disease: An Update.Journal of Parkinson's disease · 2024Review
- Behavioral analysis of motor and non-motor impairment in rodent models of Parkinson's disease.Frontiers in aging neuroscience · 2024Review
- Mechanisms of Glucocerebrosidase Dysfunction in Parkinson's Disease.Journal of molecular biology · 2023Review
- The molecular mechanism of Gaucher disease caused by compound heterozygous mutations inFrontiers in pediatrics · 2023Article
- Role of rodent models in advancing precision medicine for Parkinson's disease.Handbook of clinical neurology · 2023Review
- Lysosomal Pathogenesis of Parkinson's Disease: Insights From LRRK2 and GBA1 Rodent Models.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Human Induced Pluripotent Stem Cell Phenotyping and Preclinical Modeling of Familial Parkinson's Disease.Genes · 2022Review
- The GBA1 D409V mutation exacerbates synuclein pathology to differing extents in two alpha-synuclein models.Disease models & mechanisms · 2022Article
- Inhibition of microglial β-glucocerebrosidase hampers the microglia-mediated antioxidant and protective response in neurons.Journal of neuroinflammation · 2021Article
- 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
- Behavioral Phenotyping in a Murine Model ofInternational journal of molecular sciences · 2021Article
- The cell biology of Parkinson's disease.The Journal of cell biology · 2021Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Heterozygous mutations in glucocerebrosidase 1 (GBA1) are a major genetic risk factor for Parkinson's disease and Dementia with Lewy bodies. Mutations in GBA1 leads to GBA1 enzyme deficiency, and GBA1-associated parkinsonism has an earlier age of onset and more progressive parkinsonism. To investigate a potential influence of GBA1 deficiency caused by mutations in GBA1 on the disease progression of PD, GBA1 mice carrying D409H knock-in mutation were crossbred with the human A53T (hA53T) α-synuclein transgenic mice. Here, we show that GBA1 enzyme activity plays a significant role in the hA53T α-synuclein induced α-synucleinopathy. The expression of D409H GBA1 markedly shortens the lifespan of hA53T α-synuclein transgenic mice. Moreover, D409H GBA1 expression exacerbates the formation of insoluble aggregates of α-synuclein, glial activation, neuronal degeneration, and motor abnormalities in the hA53T α-synuclein transgenic mice. Interestingly, the expression of D409H GBA1 results in the loss of dopaminergic neurons in the substantia nigra pars compacta of hA53T transgenic mice. Taken together, these results indicate that GBA1 deficiency due to D409H mutation affects the disease onset and course in hA53T α-synuclein transgenic mice. Therefore, strategies aimed to maintain GBA1 enzyme activity could be employed to develop an effective novel therapy for GBA1 linked-PD and related α-synucleinopathies.
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