Evidence map›Paper›PMID 36454869›Full record

ArticlePloS one2022

Patient-derived three-dimensional cortical neurospheres to model Parkinson's disease.

Waseem K Raja, Esther Neves, Christopher Burke, Xin Jiang, Ping Xu, Kenneth J Rhodes, Vikram Khurana, Robert H Scannevin, Chee Yeun Chung

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.9field-weighted citation impact, top 13% of its field
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

15 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Elevation of Stearoyl-Coenzyme A Desaturase and Monounsaturated Fatty Acids in Parkinson's Disease Serum.Movement disorders : official journal of the Movement Disorder Society · 2026
    Article
  3. Article
  4. Review
  5. Review
  6. Parkinson disease is a fatty acidopathy.Nature reviews. Neurology · 2025
    Review
  7. Dysregulation of Monounsaturated Fatty Acids is Related to α-Synuclein in Multiple System Atrophy.Movement disorders : official journal of the Movement Disorder Society · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Modeling Lewy body disease withScience advances · 2024
    Article
  14. Review
  15. 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

9 authors at 2 institutions in 1 country.

Waseem K RajaYumanity Therapeutics, Boston, MA, United States of America.
Esther NevesYumanity Therapeutics, Boston, MA, United States of America.
Christopher BurkeYumanity Therapeutics, Boston, MA, United States of America.
Xin JiangYumanity Therapeutics, Boston, MA, United States of America.
Ping XuYumanity Therapeutics, Boston, MA, United States of America.
Kenneth J RhodesYumanity Therapeutics, Boston, MA, United States of America.
Vikram KhuranaDepartment of Neurology, Brigham and Women's Hospital and Harvard Medical School, Ann Romney Center for Neurologic Disease, Boston, MA, United States of America.
Robert H ScannevinYumanity Therapeutics, Boston, MA, United States of America.
Chee Yeun ChungYumanity Therapeutics, Boston, MA, United States of America.ORCID 0000-0002-5515-650X
Yumanity Therapeutics (United States) · USBroad Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

There are currently no preventive or disease-modifying therapies for Parkinson's Disease (PD). Failures in clinical trials necessitate a re-evaluation of existing pre-clinical models in order to adopt systems that better recapitulate underlying disease mechanisms and better predict clinical outcomes. In recent years, models utilizing patient-derived induced pluripotent stem cells (iPSC) have emerged as attractive models to recapitulate disease-relevant neuropathology in vitro without exogenous overexpression of disease-related pathologic proteins. Here, we utilized iPSC derived from patients with early-onset PD and dementia phenotypes that harbored either a point mutation (A53T) or multiplication at the α-synuclein/SNCA gene locus. We generated a three-dimensional (3D) cortical neurosphere culture model to better mimic the tissue microenvironment of the brain. We extensively characterized the differentiation process using quantitative PCR, Western immunoblotting and immunofluorescence staining. Differentiated and aged neurospheres revealed alterations in fatty acid profiles and elevated total and pathogenic phospho-α-synuclein levels in both A53T and the triplication lines compared to their isogenic control lines. Furthermore, treatment of the neurospheres with a small molecule inhibitor of stearoyl CoA desaturase (SCD) attenuated the protein accumulation and aberrant fatty acid profile phenotypes. Our findings suggest that the 3D cortical neurosphere model is a useful tool to interrogate targets for PD and amenable to test small molecule therapeutics.

Indexed as

Induced Pluripotent Stem CellsParkinson Diseasealpha-SynucleinFatty AcidsHumansOrganoidsalpha-SynucleinFatty Acids

Identifiers

PMID36454869
PMCPMC9714816
OpenAlexW4311068755

What OpenQuestion 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 OpenQuestion graph.