ArticleCells2022
β-Glucocerebrosidase Deficiency Activates an Aberrant Lysosome-Plasma Membrane Axis Responsible for the Onset of Neurodegeneration.
Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Sphingolipids in Gaucher disease: a systematic review.Orphanet journal of rare diseases · 2025Pooled it
- Interplay of GBA1 with lysosomal dysfunction and inflammation in Parkinson's disease.Neural regeneration research · 2026Article
- Long-term inhibition of lysosomal glucocerebrosidase activity promotes GPX4 stability and inhibits ferroptosis in dopaminergic neurons.Cell death & disease · 2026Article
- Lewy pathology formation in patient-derived GBA1 Parkinson's disease midbrain organoids.Brain : a journal of neurology · 2025Article
- Metabolic and Structural Consequences of GM3 Synthase Deficiency: Insights from an HEK293-T Knockout Model.Biomedicines · 2025Article
- Current opinion on pluripotent stem cell technology in Gaucher's disease: challenges and future prospects.Cytotechnology · 2025Review
- Clinical, mechanistic, biomarker, and therapeutic advances in GBA1-associated Parkinson's disease.Translational neurodegeneration · 2024Review
- The endolysosomal system in conventional and unconventional protein secretion.The Journal of cell biology · 2024Review
- Whole-exome sequencing reveals genetic variants that may play a role in neurocytomas.Journal of neuro-oncology · 2024Article
- Tau accumulation in degradative organelles is associated to lysosomal stress.Scientific reports · 2023Article
- Axonal Transport of Lysosomes Is Unaffected in Glucocerebrosidase-Inhibited iPSC-Derived Forebrain Neurons.eNeuro · 2023Article
- Cross-talk between CFTR and sphingolipids in cystic fibrosis.FEBS open bio · 2023Review
- Genetic Evidence for Endolysosomal Dysfunction in Parkinson's Disease: A Critical Overview.International journal of molecular sciences · 2023Review
- Peripheral inflammatory immune response differs among sporadic and familial Parkinson's disease.NPJ Parkinson's disease · 2023Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
β-glucocerebrosidase is a lysosomal hydrolase involved in the catabolism of the sphingolipid glucosylceramide. Biallelic loss of function mutations in this enzyme are responsible for the onset of Gaucher disease, while monoallelic β-glucocerebrosidase mutations represent the first genetic risk factor for Parkinson's disease. Despite this evidence, the molecular mechanism linking the impairment in β-glucocerebrosidase activity with the onset of neurodegeneration in still unknown. In this frame, we developed two in vitro neuronal models of β-glucocerebrosidase deficiency, represented by mouse cerebellar granule neurons and human-induced pluripotent stem cells-derived dopaminergic neurons treated with the specific β-glucocerebrosidase inhibitor conduritol B epoxide. Neurons deficient for β-glucocerebrosidase activity showed a lysosomal accumulation of glucosylceramide and the onset of neuronal damage. Moreover, we found that neurons react to the lysosomal impairment by the induction of their biogenesis and exocytosis. This latter event was responsible for glucosylceramide accumulation also at the plasma membrane level, with an alteration in lipid and protein composition of specific signaling microdomains. Collectively, our data suggest that β-glucocerebrosidase loss of function impairs the lysosomal compartment, establishing a lysosome-plasma membrane axis responsible for modifications in the plasma membrane architecture and possible alterations of intracellular signaling pathways, leading to neuronal damage.
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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.