ArticleDisease models & mechanisms2022
The GBA1 D409V mutation exacerbates synuclein pathology to differing extents in two alpha-synuclein models.
Article in Disease models & mechanisms, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Intra-CNS AAV9-Molecular therapy. Advances · 2026Article
- Sphingolipidoses: expanding the spectrum of α-synucleinopathies.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Pharmacological inhibition of O-GlcNAcase reduces pS129-α-synuclein positive aggregates in the substantia nigra of mThy1-hSNCA mice.Journal of Parkinson's disease · 2026Article
- Human Wild-Type α-Synuclein Drives Progressive Tau Pathology in a Disease-Relevant Mouse Model of Synucleinopathy.Research square · 2025Article
- Imbalanced mitochondrial dynamics in human PD and α-synuclein mouse brains.Neurobiology of disease · 2025Article
- Bridging the gap: investigating the role of phosphorylation at the serine 129 site of α-synuclein in VAPB-PTPIP51 interactions.Acta neuropathologica communications · 2025Article
- Therapeutic Role of Heterocyclic Compounds in Neurodegenerative Diseases: Insights from Alzheimer's and Parkinson's Diseases.Neurology international · 2025Review
- Mitochondrial oxidant stress promotes α-synuclein aggregation and spreading in mice with mutated glucocerebrosidase.NPJ Parkinson's disease · 2024Article
- Olfactory deficit and gastrointestinal dysfunction precede motor abnormalities in alpha-Synuclein G51D knock-in mice.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Neither alpha-synuclein fibril strain nor host murine genotype influences seeding efficacy.NPJ Parkinson's disease · 2024Article
- Live cellFrontiers in cellular neuroscience · 2023Article
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13 authors.
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Abstract
Heterozygous mutations in the GBA1 gene - encoding lysosomal glucocerebrosidase (GCase) - are the most common genetic risk factors for Parkinson's disease (PD). Experimental evidence suggests a correlation between decreased GCase activity and accumulation of alpha-synuclein (aSyn). To enable a better understanding of the relationship between aSyn and GCase activity, we developed and characterized two mouse models that investigate aSyn pathology in the context of reduced GCase activity. The first model used constitutive overexpression of wild-type human aSyn in the context of the homozygous GCase activity-reducing D409V mutant form of GBA1. Although increased aSyn pathology and grip strength reductions were observed in this model, the nigrostriatal system remained largely intact. The second model involved injection of aSyn preformed fibrils (PFFs) into the striatum of the homozygous GBA1 D409V knock-in mouse model. The GBA1 D409V mutation did not exacerbate the pathology induced by aSyn PFF injection. This study sheds light on the relationship between aSyn and GCase in mouse models, highlighting the impact of model design on the ability to model a relationship between these proteins in PD-related pathology.
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