ArticleAnnals of neurology2021
Lewy Body-like Inclusions in Human Midbrain Organoids Carrying Glucocerebrosidase and α-Synuclein Mutations.
Article in Annals of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled 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.
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
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Organoids: Key advances, optimization, and technological iterations in their application to neurodegenerative diseases.Neural regeneration research · 2026Article
- Stem cell derived neural organoid approaches for neurological diseases.Neural regeneration research · 2026Article
- Review
- Rodent models and accompanying in vitro strategies for studying the etiology and therapy of Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Neuroinflammation in Alzheimer's and Parkinson's diseases: pathogenic mechanisms and therapeutic strategies.Translational neurodegeneration · 2026Review
- Advances and applications of brain organoids in central nervous system disorders: Bridging the gap from laboratory to clinic.Neural regeneration research · 2026Article
- Article
- Parkinson's Disease Patient-Specific Striatum Organoids Show Hallmarks of Increased Inflammation.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Autophagy dysfunction in iPSCs-derived neurons and midbrain organoids carrying a SNCA triplication.NPJ Parkinson's disease · 2026Article
- Autophagy Activators Normalize Aberrant Tau Proteostasis and Rescue Synapses in Human Familial Alzheimer's Disease iPSC-Derived Cortical Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Single-cell transcriptomics revealed molecular vulnerability in a human midbrain-like organoid model of Parkinson's disease.iScience · 2026Article
- Advances in the pathophysiological study of brain development: application of cerebral organoid combined with Spatial omics technology.Stem cell research & therapy · 2026Review
- From microfluidics to nanodelivery: artificial intelligence reshapes neuropharmacology research strategies.Frontiers in pharmacology · 2026Review
- Single-cell sequencing and organoids: applications in organ development and disease.Molecular biomedicine · 2025Review
- Alpha-Synuclein Neurobiology in Parkinson's Disease: A Comprehensive Review of Its Role, Mechanisms, and Therapeutic Perspectives.Brain sciences · 2025Review
- Genetic Manipulation in Organoid Models and Their Applications in Central Nervous System Pathologies.Molecular neurobiology · 2025Review
- Three-dimensional midbrain organoids: a next-generation tool for Parkinson's disease modelling and drug discovery.Stem cell research & therapy · 2025Review
- Article
- Human Pluripotent Stem Cell-Derived Skeletal Muscle Organoid Model of Aging-Induced Sarcopenia.Journal of cachexia, sarcopenia and muscle · 2025Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveWe utilized human midbrain-like organoids (hMLOs) generated from human pluripotent stem cells carrying glucocerebrosidase gene (GBA1) and α-synuclein (α-syn; SNCA) perturbations to investigate genotype-to-phenotype relationships in Parkinson disease, with the particular aim of recapitulating α-syn- and Lewy body-related pathologies and the process of neurodegeneration in the hMLO model.
methodsWe generated and characterized hMLOs from GBA1
resultsWe identified for the first time that the loss of glucocerebrosidase, coupled with wild-type α-syn overexpression, results in a substantial accumulation of detergent-resistant, β-sheet-rich α-syn aggregates and Lewy body-like inclusions in hMLOs. These Lewy body-like inclusions exhibit a spherically symmetric morphology with an eosinophilic core, containing α-syn with ubiquitin, and can also be formed in Parkinson disease patient-derived hMLOs. We also demonstrate that impaired glucocerebrosidase function promotes the formation of Lewy body-like inclusions in hMLOs derived from patients carrying the SNCA triplication.
interpretationTaken together, the data indicate that our hMLOs harboring 2 major risk factors (glucocerebrosidase deficiency and wild-type α-syn overproduction) of Parkinson disease provide a tractable model to further elucidate the underlying mechanisms for progressive Lewy body formation. ANN NEUROL 2021;90:490-505.
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.