ArticleNeurobiology of disease2020
Glucocerebrosidase activity, cathepsin D and monomeric α-synuclein interactions in a stem cell derived neuronal model of a PD associated GBA1 mutation.
Article in Neurobiology of disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 54 citations in OpenAlex.
- Rare-Variant Burden across Lysosomal Genes Implicates Sialylation and Ganglioside Metabolism in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Glucocerebrosidase dysfunction in GBA1 carriers: insights from blood and macrophage analyses.Molecular biology reports · 2026Article
- Shared and distinct lipid profiles in amygdala from sporadic and GBA-associated Parkinson's diseases.NPJ Parkinson's disease · 2026Article
- LRRK2 I1371V Mutation Drives Astrocytic Glucose Metabolism Failure and Induces Integrated ER-Mitochondria-Lysosome Dysfunction in Parkinson's Disease.International journal of molecular sciences · 2026Article
- Rare-variant burden across lysosomal genes implicates sialylation and ganglioside metabolism in Parkinson's disease.medRxiv : the preprint server for health sciences · 2026Article
- Calcium modulating ligand confers risk for Parkinson's disease and impacts lysosomes.Annals of clinical and translational neurology · 2025Article
- The role of alpha-synuclein in synucleinopathy: Impact on lipid regulation at mitochondria-ER membranes.NPJ Parkinson's disease · 2025Article
- Review
- Consensus Guidance for Genetic Counseling in GBA1 Variants: A Focus on Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2024Review
- The Molecular Impact of Glucosylceramidase Beta 1 (Gba1) in Parkinson's Disease: a New Genetic State of the Art.Molecular neurobiology · 2024Review
- Review
- Synaptic dysfunction and extracellular matrix dysregulation in dopaminergic neurons from sporadic and E326K-GBA1 Parkinson's disease patients.NPJ Parkinson's disease · 2024Article
- Post-translational proteomics platform identifies neurite outgrowth impairments in Parkinson's disease GBA-N370S dopamine neurons.Cell reports · 2023Article
- Biochemical Characteristics of iPSC-Derived Dopaminergic Neurons from N370SInternational journal of molecular sciences · 2023Article
- The GBA variant E326K is associated with alpha-synuclein aggregation and lipid droplet accumulation in human cell lines.Human molecular genetics · 2023Article
- Review
- Review
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- Deregulation of mTORC1-TFEB axis in human iPSC model ofFrontiers in neuroscience · 2023Article
- Live cellFrontiers in cellular neuroscience · 2023Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The presence of GBA1 gene mutations increases risk for Parkinson's disease (PD), but the pathogenic mechanisms of GBA1 associated PD remain unknown. Given that impaired α-synuclein turnover is a hallmark of PD pathogenesis and cathepsin D is a key enzyme involved in α-synuclein degradation in neuronal cells, we have examined the relationship of glucocerebrosidase (GCase), cathepsin D and monomeric α-synuclein in human neural crest stem cell derived dopaminergic neurons. We found that normal activity of GCase is necessary for cathepsin D to perform its function of monomeric α-synuclein removal from neurons. GBA1 mutations lead to a lower level of cathepsin D protein and activity, and higher level of monomeric α-synuclein in neurons. When GBA1 mutant neurons were treated with GCase replacement or chaperone therapy; cathepsin D protein levels and activity were restored, and monomeric α-synuclein decreased. When cathepsin D was inhibited, GCase replacement failed to reduce monomeric α-synuclein levels in GBA1 mutant neurons. These data indicate that GBA1 gene mutations increase monomeric α-synuclein levels via an effect on lysosomal cathepsin D in neurons.
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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.