Evidence map›Paper›PMID 41053297›Full record

ArticleCommunications biology2025

Novel regulators of heparan sulfate proteoglycans modulate cellular uptake of α-synuclein fibrils.

Benoît Vanderperre, Amitha Muraleedharan, Marie-France Dorion, Frédérique Larroquette, Esther Del Cid Pellitero, Nishani Rajakulendran, Carol X-Q Chen, Roxanne Larivière, Charlotte Michaud-Tardif, Thomas Goiran and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

27 authors.

Benoît Vanderperre *Département des Sciences biologiques, Université du Québec à Montréal, Montréal, QC, Canada. vanderperre.benoit@uqam.ca.ORCID http://orcid.org/0000-0002-2111-1071
Amitha Muraleedharan *Département des Sciences biologiques, Université du Québec à Montréal, Montréal, QC, Canada.
Marie-France DorionThe Neuro's Early Drug Discovery Unit (EDDU), Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Montréal, QC, Canada.ORCID http://orcid.org/0000-0003-1285-6087
Frédérique LarroquetteMcGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, QC, Canada.
Esther Del Cid PelliteroMcGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, QC, Canada.ORCID http://orcid.org/0000-0001-8658-944X
Nishani RajakulendranLeslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
Carol X-Q ChenThe Neuro's Early Drug Discovery Unit (EDDU), Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Montréal, QC, Canada.
Roxanne LarivièreMcGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, QC, Canada.
Charlotte Michaud-TardifMcGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, QC, Canada.
Thomas GoiranMcGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, QC, Canada.
Rony ChidiacLeslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
Damien LipumaDépartement des Sciences biologiques, Université du Québec à Montréal, Montréal, QC, Canada.
Graham MacLeodLeslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
Rhalena ThomasMcGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, QC, Canada.ORCID http://orcid.org/0000-0002-5396-7587
Zhangjie WangDivision of Chemical Biology & Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Wolfgang E ReintschThe Neuro's Early Drug Discovery Unit (EDDU), Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Montréal, QC, Canada.
Wen LuoThe Neuro's Early Drug Discovery Unit (EDDU), Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Montréal, QC, Canada.ORCID http://orcid.org/0000-0003-1785-9615
Irina ShlaiferThe Neuro's Early Drug Discovery Unit (EDDU), Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Montréal, QC, Canada.ORCID http://orcid.org/0000-0002-3737-268X
Fuming ZhangDepartment of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY, USA.ORCID http://orcid.org/0000-0003-2803-3704
Ke XiaDepartment of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY, USA.
Zachary SteinhartLeslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
Robert J LinhardtDepartment of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY, USA.ORCID http://orcid.org/0000-0003-2219-5833
Jean-François TrempeDepartment of Pharmacology & Therapeutics and Centre de Recherche en Biologie Structurale, McGill University, Montréal, QC, Canada.ORCID http://orcid.org/0000-0002-6543-3371
Jian LiuDivision of Chemical Biology & Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Thomas M DurcanThe Neuro's Early Drug Discovery Unit (EDDU), Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Montréal, QC, Canada.
Stephane AngersLeslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.ORCID http://orcid.org/0000-0001-7241-9044
Edward A FonMcGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, QC, Canada. ted.fon@mcgill.ca.ORCID http://orcid.org/0000-0002-5520-6239

Funding

Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) Canada Research Chair (Tier 1) in Parkinson's diseaseGouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) MFE-152571Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation) 021129
6 · The paper itself

Abstract

Synucleinopathies are characterized by the accumulation and propagation of α-synuclein (α-syn) aggregates throughout the brain, leading to neuronal dysfunction and death. In this study, we used an unbiased FACS-based genome-wide CRISPR/Cas9 knockout screening to identify genes that regulate the entry and accumulation of α-syn preformed fibrils (PFFs) in cells. We identified key genes and pathways specifically implicated in α-syn PFFs intracellular accumulation, including heparan sulfate proteoglycans (HSPG) biosynthesis and Golgi trafficking. All confirmed hits affected heparan sulfate (HS), a post-translational modification known to act as a receptor for proteinaceous aggregates including α-syn and tau. Intriguingly, deletion of SLC39A9 and C3orf58 genes, encoding respectively a Golgi-localized exporter of Zn

Indexed as

alpha-SynucleinHeparan Sulfate ProteoglycansAnimalsCation Transport ProteinsCRISPR-Cas SystemsGolgi ApparatusHumansMicealpha-SynucleinCation Transport ProteinsHeparan Sulfate Proteoglycans

Identifiers

PMID41053297
PMCPMC12501064

What OpenQuestion holds

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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.