Evidence map›Paper›PMID 40917882›Full record

ArticleiScience2025

An iPSC-derived neuronal model reveals manganese's role in neuronal endocytosis, calcium flux and mitochondrial bioenergetics.

Dimitri Budinger, Sharmin Alhaque, Ramón González-Méndez, Chris Dadswell, Katy Barwick, Arianna Ferrini, Charlotte Roth, Conor J McCann, Karin Tuschl, Fatma Al Jasmi and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. 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

19 authors.

Dimitri BudingerDepartment of Developmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, Great Ormond Street Institute of Child Health, University College London, London, UK.
Sharmin AlhaqueDepartment of Developmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, Great Ormond Street Institute of Child Health, University College London, London, UK.
Ramón González-MéndezSchool of Life Sciences, University of Sussex, Brighton, UK.
Chris DadswellSchool of Life Sciences, University of Sussex, Brighton, UK.
Katy BarwickDepartment of Developmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, Great Ormond Street Institute of Child Health, University College London, London, UK.
Arianna FerriniDepartment of Developmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, Great Ormond Street Institute of Child Health, University College London, London, UK.
Charlotte RothDepartment of Developmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, Great Ormond Street Institute of Child Health, University College London, London, UK.
Conor J McCannDepartment of Cell and Developmental Biology, University College London, London, UK.
Karin TuschlGenetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London, UK.
Fatma Al JasmiDepartment of Genetics & Genomics, College of Medicine and Health Science, United Arab Emirates University, Al Ain, UAE.
Maha S ZakiClinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.
Julien H ParkUniversity Hospital Münster, Department of General Paediatrics, Münster, Germany.
Russell C DaleChildren's Hospital at Westmead University of Sydney, Sydney, NSW, Australia.
Shekeeb MohammadChildren's Hospital at Westmead University of Sydney, Sydney, NSW, Australia.
John ChristodoulouMurdoch Childrens Research Institute, The Royal Children's Hospital and Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.
Dale MouldingDepartment of Developmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, Great Ormond Street Institute of Child Health, University College London, London, UK.
Michael R DuchenDepartment of Cell and Developmental Biology, University College London, London, UK.
Serena BarralDepartment of Developmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, Great Ormond Street Institute of Child Health, University College London, London, UK.
Manju A KurianDepartment of Developmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, Great Ormond Street Institute of Child Health, University College London, London, UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Manganese (Mn) is an essential trace metal required for normal biological function, yet it also poses neurotoxic risks when dysregulated. Maintaining proper intracellular and extracellular Mn levels is critical, as Mn imbalance has been implicated in a spectrum of human diseases-including inherited Mn transport disorders, acquired manganism, and more prevalent neurodegenerative diseases such as Parkinson's and Alzheimer's disease. Despite these associations, the cellular mechanisms driving Mn-induced neuropathology remain poorly understood. To investigate this, we developed an induced pluripotent stem cell (iPSC)-derived midbrain neuronal model using patient lines with mutations in SLC39A14, SLC39A8, and SLC30A10. Through integrated transcriptomic and functional analyses, we found that Mn dyshomeostasis disrupts essential neuronal pathways, including mitochondrial bioenergetics, calcium signaling, endocytosis, glycosylation, and stress responses-leading to early neurodegeneration. This humanized model advances our understanding of Mn's impact on neuronal health and disease and highlights potential molecular targets for future therapeutic interventions in Mn-related neurological disorders.

Indexed as

Cell biologyMolecular biologyNeuroscience

Identifiers

PMID40917882
PMCPMC12410566

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Registered trials

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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.