ArticleBrain : a journal of neurology2017
The L444P Gba1 mutation enhances alpha-synuclein induced loss of nigral dopaminergic neurons in mice.
Article in Brain : a journal of neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- A bibliometric analysis of alpha-synuclein in Parkinson's disease from 2015 to 2024.Frontiers in neurologyPooled it
- Understanding the genetic imperfections of Lewy body dementia.Molecular neurodegeneration · 2026Review
- Sphingolipidoses: expanding the spectrum of α-synucleinopathies.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- GBA1 F213I mutation increases the expression of LCN2 promoting neurodegeneration.Cell death and differentiation · 2026Article
- 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
- Underlying Mechanisms of GBA1 in Parkinson's Disease and Dementia with Lewy Bodies: Narrative Review.Genes · 2025Review
- Metabolic reprogramming and altered ATP content impair neuroprotective functions of microglia in β-glucocerebrosidase deficiency models.Journal of neuroinflammation · 2025Article
- Elevated hexosylceramides in Parkinson's disease cause gene upregulations in neurons mimicking responses to pathogens.NPJ Parkinson's disease · 2025Article
- Classification of GBA1 variants and their impact on Parkinson's disease: an in silico score analysis.NPJ Parkinson's disease · 2025Article
- Stearoyl-CoA desaturase inhibition normalizes brain lipid saturation, α-synuclein homeostasis, and motor function in mutant Gba1-Parkinson mice.JCI insight · 2025Article
- Synaptic and cognitive impairment associated with L444P heterozygous glucocerebrosidase mutation.Brain : a journal of neurology · 2025Article
- Nanosensor-based imaging of realtime dopamine release in neurons derived from iPSCs of patients with Parkinson's disease.Materials today. Bio · 2025Article
- Mitochondrial oxidant stress promotes α-synuclein aggregation and spreading in mice with mutated glucocerebrosidase.NPJ Parkinson's disease · 2024Article
- Clinical, mechanistic, biomarker, and therapeutic advances in GBA1-associated Parkinson's disease.Translational neurodegeneration · 2024Review
- Inhibition of cysteine protease cathepsin L increases the level and activity of lysosomal glucocerebrosidase.JCI insight · 2024Article
- Recalibrating the Why and Whom of Animal Models in Parkinson Disease: A Clinician's Perspective.Brain sciences · 2024Review
- Advancements in Genetic and Biochemical Insights: Unraveling the Etiopathogenesis of Neurodegeneration in Parkinson's Disease.Biomolecules · 2024Review
- The AAV-α-Synuclein Model of Parkinson's Disease: An Update.Journal of Parkinson's disease · 2024Review
- Animal models of Parkinson's disease: bridging the gap between disease hallmarks and research questions.Translational neurodegeneration · 2023Review
- Biochemical Characteristics of iPSC-Derived Dopaminergic Neurons from N370SInternational journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Mutations in glucocerebrosidase 1 (GBA1) represent the most prevalent risk factor for Parkinson's disease. The molecular mechanisms underlying the link between GBA1 mutations and Parkinson's disease are incompletely understood. We analysed two aged (24-month-old) Gba1 mouse models, one carrying a knock-out mutation and the other a L444P knock-in mutation. A significant reduction of glucocerebrosidase activity was associated with increased total alpha-synuclein accumulation in both these models. Gba1 mutations alone did not alter the number of nigral dopaminergic neurons nor striatal dopamine levels. We then investigated the effect of overexpression of human alpha-synuclein in the substantia nigra of aged (18 to 21-month-old) L444P Gba1 mice. Following intraparenchymal injections of human alpha-synuclein carrying viral vectors, pathological accumulation of phosphorylated alpha-synuclein occurred within the transduced neurons. Stereological counts of nigral dopaminergic neurons revealed a significantly greater cell loss in Gba1-mutant than wild-type mice. These results indicate that Gba1 deficiency enhances neuronal vulnerability to neurodegenerative processes triggered by increased alpha-synuclein expression.
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Registered trials
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.