ArticleNature communications2023
Targeting neuronal lysosomal dysfunction caused by β-glucocerebrosidase deficiency with an enzyme-based brain shuttle construct.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Cellular and signalling mechanisms that regulate the blood-brain barrier.Nature reviews. Molecular cell biology · 2026Review
- Mannose-6-Phosphate-Tagged Liposomes Exhibit Increased Transcytosis Across Human Blood-Brain Barrier Model.Pharmaceutics · 2026Article
- Pathological Protein Targets in Parkinson's Disease: Progress Towards the Development of Disease-Modifying Therapies.CNS drugs · 2026Review
- Urine bis(Monoacylglycerol)Phosphate and risk of freezing of gait in parkinson's disease.Scientific reports · 2026Article
- Crossing the barrier: nanomedicine as a frontier therapy for neuropathic Gaucher disease type 3.Annals of medicine and surgery (2012) · 2026Article
- Cellular Senescence and SASP in Bladder Ageing: Mechanisms and Emerging Interventions.International journal of general medicine · 2026Review
- C-COMPASS: a user-friendly neural network tool profiles cell compartments at protein and lipid levels.Nature methods · 2026Article
- Biodistribution of AAV1, AAV5, AAV9, and AAVDJ serotypes after intra-cisterna magna delivery in non-human primates.Molecular therapy. Methods & clinical development · 2025Article
- Article
- A novel peptide-based strategy to enhance GBA1 expression for treating Parkinson's disease.NPJ Parkinson's disease · 2025Article
- C-terminus-dependent detection of lysosomal alpha-synuclein in nigral Parkinson's disease human brain neurons.Molecular neurodegeneration · 2025Article
- Enzyme Activity-Based Genome-wide Screening for Modifiers of Lysosomal Glucocerebrosidase Uncovers Candidate Risk Factors for Parkinson's Disease.ACS central science · 2025Article
- Bispecific brain-penetrant antibodies for treatment of Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Review
- Review
- Fc-engineered large molecules targeting blood-brain barrier transferrin receptor and CD98hc have distinct central nervous system and peripheral biodistribution.Nature communications · 2025Article
- Deletion of Gba in neurons, but not microglia, causes neurodegeneration in a Gaucher mouse model.JCI insight · 2024Article
- High-throughput screening for small-molecule stabilizers of misfolded glucocerebrosidase in Gaucher disease and Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Therapeutic delivery of recombinant glucocerebrosidase enzyme-containing extracellular vesicles to human cells from Gaucher disease patients.Orphanet journal of rare diseases · 2024Article
- Clinical, mechanistic, biomarker, and therapeutic advances in GBA1-associated Parkinson's disease.Translational neurodegeneration · 2024Review
- Gaucher disease provides a unique window into Parkinson disease pathogenesis.Nature reviews. Neurology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 5 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in glucocerebrosidase cause the lysosomal storage disorder Gaucher's disease and are the most common risk factor for Parkinson's disease. Therapies to restore the enzyme's function in the brain hold great promise for treating the neurological implications. Thus, we developed blood-brain barrier penetrant therapeutic molecules by fusing transferrin receptor-binding moieties to β-glucocerebrosidase (referred to as GCase-BS). We demonstrate that these fusion proteins show significantly increased uptake and lysosomal efficiency compared to the enzyme alone. In a cellular disease model, GCase-BS rapidly rescues the lysosomal proteome and lipid accumulations beyond known substrates. In a mouse disease model, intravenous injection of GCase-BS leads to a sustained reduction of glucosylsphingosine and can lower neurofilament-light chain plasma levels. Collectively, these findings demonstrate the potential of GCase-BS for treating GBA1-associated lysosomal dysfunction, provide insight into candidate biomarkers, and may ultimately open a promising treatment paradigm for lysosomal storage diseases extending beyond the central nervous system.
Indexed as
Identifiers
What OpenQuestion holds
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.