Evidence mapPaperPMID 39388267Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2024

High-throughput screening for small-molecule stabilizers of misfolded glucocerebrosidase in Gaucher disease and Parkinson's disease.

Darian Williams, Logan M Glasstetter, Tiffany T Jong, Tiffany Chen, Abhijeet Kapoor, Sha Zhu, Yanping Zhu, Raul Calvo, Alexandra Gehrlein, Kimberly Wong and 7 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. The Race to Salvage Glucocerebrosidase: Understanding Small-Molecule Therapies for GBA1-Associated Parkinsonism.Movement disorders : official journal of the Movement Disorder Society · 2026
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. An Overview of Gaucher Disease.Diagnostics (Basel, Switzerland) · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Darian Williams *Division of Preclinical Innovation, National Center for Advancing Translational Sciences, NIH, Rockville, MD 20850.
Logan M Glasstetter *Molecular Neurogenetics Section, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892.
Tiffany T Jong *Molecular Neurogenetics Section, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892.
Tiffany ChenMolecular Neurogenetics Section, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892.ORCID 0009-0007-9297-1988
Abhijeet KapoorDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, NIH, Rockville, MD 20850.
Sha ZhuDepartment of Chemistry, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.ORCID 0000-0003-3352-1040
Yanping ZhuDepartment of Chemistry, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
Raul CalvoDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, NIH, Rockville, MD 20850.ORCID 0000-0001-5967-1296
Alexandra GehrleinRoche Pharma Research and Early Development, Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, 4070 Basel, Switzerland.ORCID 0000-0003-4901-7316
Kimberly WongMolecular Neurogenetics Section, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892.ORCID 0009-0006-8865-9660
Andrew N HoganMolecular Neurogenetics Section, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892.
David J VocadloDepartment of Chemistry, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.ORCID 0000-0001-6897-5558
Ravi JagasiaRoche Pharma Research and Early Development, Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, 4070 Basel, Switzerland.
Juan J MaruganDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, NIH, Rockville, MD 20850.ORCID 0000-0002-3951-7061
Ellen SidranskyMolecular Neurogenetics Section, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892.ORCID 0000-0002-3019-8500
Mark J HendersonDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, NIH, Rockville, MD 20850.ORCID 0000-0001-8590-7338
Yu ChenMolecular Neurogenetics Section, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892.ORCID 0000-0001-5438-7309

Funding

Michael J. Fox Foundation for Parkinson's Research (MJFF) MJFF-021673
6 · The paper itself

Abstract

Glucocerebrosidase (GCase) is implicated in both a rare, monogenic disorder (Gaucher disease, GD) and a common, multifactorial condition (Parkinson's disease, PD); hence, it is an urgent therapeutic target. To identify correctors of severe protein misfolding and trafficking obstruction manifested by the pathogenic L444P-variant of GCase, we developed a suite of quantitative, high-throughput, cell-based assays. First, we labeled GCase with a small proluminescent HiBiT peptide reporter tag, enabling quantitation of protein stabilization in cells while faithfully maintaining target biology. TALEN-based gene editing allowed for stable integration of a single HiBiT-

Indexed as

Gaucher DiseaseGlucosylceramidaseHigh-Throughput Screening AssaysParkinson DiseaseProtein FoldingCell Line, TumorHumansSmall Molecule LibrariesGlucosylceramidaseSmall Molecule LibrariesGaucher diseaseglucocerebrosidasehigh-throughput screeningParkinson’s diseasepharmacological chaperone

Identifiers

PMID39388267
PMCPMC11494340

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.