Evidence map›Paper›PMID 36870058›Full record

ArticleCell reports2023

Post-translational proteomics platform identifies neurite outgrowth impairments in Parkinson's disease GBA-N370S dopamine neurons.

Helle Bogetofte, Brent J Ryan, Pia Jensen, Sissel I Schmidt, Dana L E Vergoossen, Mike B Barnkob, Lisa N Kiani, Uroosa Chughtai, Rachel Heon-Roberts, Maria Claudia Caiazza and 13 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
6.1field-weighted citation impact, top 3% 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

26 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
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  6. Post-translational modifications in CD8Frontiers in immunology · 2026
    Review
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  8. Article
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  12. Proteomic insights into the biology of dopaminergic neurons.Frontiers in molecular neuroscience · 2025
    Review
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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

23 authors at 2 institutions in 2 countries.

Helle BogetofteOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK; Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense C, Denmark; Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
Brent J RyanOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK. Electronic address: brent.ryan@dpag.ox.ac.uk.
Pia JensenDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
Sissel I SchmidtOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK; Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense C, Denmark.
Dana L E VergoossenOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK.
Mike B BarnkobCentre for Cellular Immunotherapy of Haematological Cancer Odense (CITCO), Department of Clinical Immunology, Odense University Hospital, University of Southern Denmark, 5000 Odense C, Denmark.
Lisa N KianiOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK.
Uroosa ChughtaiOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK.
Rachel Heon-RobertsOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.
Maria Claudia CaiazzaOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.
William McGuinnessOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.
Ricardo Márquez-GómezOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.
Jane VowlesJames Martin Stem Cell Facility, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
Fiona S BunnOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK.
Janine BrandesOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK.
Peter KilfeatherOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.
Jack P ConnorOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.
Hugo J R FernandesOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.
Tara M CaffreyOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK.
Morten MeyerDepartment of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense C, Denmark; Department of Neurology, Odense University Hospital, 5000 Odense C, Denmark.
Sally A CowleyJames Martin Stem Cell Facility, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
Martin R LarsenDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
Richard Wade-MartinsOxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK. Electronic address: richard.wade-martins@dpag.ox.ac.uk.
University of Oxford · GBUniversity of Southern Denmark · DK

Funding

Medical Research Council G0900747Medical Research Council G0900747 91070Medical Research Council MR/N013255/1Wellcome Trust 090532Wellcome Trust 090532/Z/09/ZWellcome Trust WTISSF121302
6 · The paper itself

Abstract

Variants at the GBA locus, encoding glucocerebrosidase, are the strongest common genetic risk factor for Parkinson's disease (PD). To understand GBA-related disease mechanisms, we use a multi-part-enrichment proteomics and post-translational modification (PTM) workflow, identifying large numbers of dysregulated proteins and PTMs in heterozygous GBA-N370S PD patient induced pluripotent stem cell (iPSC) dopamine neurons. Alterations in glycosylation status show disturbances in the autophagy-lysosomal pathway, which concur with upstream perturbations in mammalian target of rapamycin (mTOR) activation in GBA-PD neurons. Several native and modified proteins encoded by PD-associated genes are dysregulated in GBA-PD neurons. Integrated pathway analysis reveals impaired neuritogenesis in GBA-PD neurons and identify tau as a key pathway mediator. Functional assays confirm neurite outgrowth deficits and identify impaired mitochondrial movement in GBA-PD neurons. Furthermore, pharmacological rescue of glucocerebrosidase activity in GBA-PD neurons improves the neurite outgrowth deficit. Overall, this study demonstrates the potential of PTMomics to elucidate neurodegeneration-associated pathways and potential drug targets in complex disease models.

Indexed as

Parkinson DiseaseDopaminergic NeuronsGlucosylceramidaseHumansMutationNeuronal OutgrowthProtein Processing, Post-TranslationalProteomicsGBA protein, humanGlucosylceramidaseCP: NeuroscienceglucocerebrosidaseglycosylationiPSClysosomeneuritogenesisParkinson’sphosphoproteomicspost-translational modificationsproteomicsstem cells

Identifiers

PMID36870058
PMCPMC7617855
OpenAlexW4322764335

What OpenQuestion holds

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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.