Evidence map›Paper›PMID 40563111›Full record

ArticleActa neuropathologica communications2025

Copper supplementation mitigates Parkinson-like wild-type SOD1 pathology and nigrostriatal degeneration in a novel mouse model.

Benjamin D Rowlands, Benjamin G Trist, Connor Karozis, Greta Schaffer, David Mor, Richard Harwood, Sarah A Rosolen, Veronica Cottam, Freyja Persson-Carboni, Miriam Richardson and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Proteomic Exploration of L1CAMInternational journal of molecular sciences · 2025
    Article
  4. Article
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

15 authors.

Benjamin D Rowlands *Brain and Mind Centre, School of Medical Sciences (Neuroscience), Faculty of Medicine and Health, The University of Sydney, 94-100 Mallett Street, Camperdown, NSW, 2050, Australia.
Benjamin G Trist *Brain and Mind Centre, School of Medical Sciences (Neuroscience), Faculty of Medicine and Health, The University of Sydney, 94-100 Mallett Street, Camperdown, NSW, 2050, Australia.
Connor KarozisBrain and Mind Centre, School of Medical Sciences (Neuroscience), Faculty of Medicine and Health, The University of Sydney, 94-100 Mallett Street, Camperdown, NSW, 2050, Australia.
Greta SchafferBrain and Mind Centre, School of Medical Sciences (Neuroscience), Faculty of Medicine and Health, The University of Sydney, 94-100 Mallett Street, Camperdown, NSW, 2050, Australia.
David MorBrain and Mind Centre, School of Medical Sciences (Neuroscience), Faculty of Medicine and Health, The University of Sydney, 94-100 Mallett Street, Camperdown, NSW, 2050, Australia.
Richard HarwoodSydney Microscopy and Microanalysis, The University of Sydney, Sydney, NSW, 2006, Australia.
Sarah A RosolenBrain and Mind Centre, School of Medical Sciences (Neuroscience), Faculty of Medicine and Health, The University of Sydney, 94-100 Mallett Street, Camperdown, NSW, 2050, Australia.
Veronica CottamBrain and Mind Centre, School of Medical Sciences (Neuroscience), Faculty of Medicine and Health, The University of Sydney, 94-100 Mallett Street, Camperdown, NSW, 2050, Australia.
Freyja Persson-CarboniBrain and Mind Centre, School of Medical Sciences (Neuroscience), Faculty of Medicine and Health, The University of Sydney, 94-100 Mallett Street, Camperdown, NSW, 2050, Australia.
Miriam RichardsonBrain and Mind Centre, School of Medical Sciences (Neuroscience), Faculty of Medicine and Health, The University of Sydney, 94-100 Mallett Street, Camperdown, NSW, 2050, Australia.
Anne A LiBrain and Mind Centre, School of Medical Sciences (Neuroscience), Faculty of Medicine and Health, The University of Sydney, 94-100 Mallett Street, Camperdown, NSW, 2050, Australia.
Michael P GotsbacherSchool of Medical Sciences (Molecular Biomedicine), Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2006, Australia.
Amr H AbdeenBrain and Mind Centre, School of Medical Sciences (Neuroscience), Faculty of Medicine and Health, The University of Sydney, 94-100 Mallett Street, Camperdown, NSW, 2050, Australia.
Rachel CoddSchool of Medical Sciences (Molecular Biomedicine), Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2006, Australia.
Kay L DoubleBrain and Mind Centre, School of Medical Sciences (Neuroscience), Faculty of Medicine and Health, The University of Sydney, 94-100 Mallett Street, Camperdown, NSW, 2050, Australia. kay.double@sydney.edu.au.

Funding

Michael J. Fox Foundation for Parkinson's Research MJFF-009200National Health and Medical Research Council APP1181864
6 · The paper itself

Abstract

Misfolded wild-type superoxide dismutase 1 (disSOD1) protein is implicated in the death of substantia nigra (SN) dopamine neurons in Parkinson disease. Regionally reduced copper availability, and subsequent reduced copper binding to SOD1, is a key factor driving the development of this pathology, suggesting brain copper supplementation may constitute an effective means of preventing its formation. We evaluated whether the blood-brain-barrier-permeable copper delivery drug, CuATSM, attenuated the misfolding and deposition of wild-type disSOD1 and associated neuron death in a novel mouse model that expresses this pathology. These factors were profiled using proteomic and elemental mass spectrometry, together with biochemical and histological workflows. We demonstrated copper supplementation corrects altered post-translational modifications on soluble SOD1 and improves the enzymatic activity of the protein in the brains of these animals. These changes were associated with a significant reduction in disSOD1 pathology and preservation of dopamine neurons in the SN, which were highly correlated with tissue copper levels. Our data position wild-type disSOD1 pathology as a novel drug target for Parkinson disease and suggest that brain copper supplementation may constitute an effective means of slowing SN dopamine neuron death in this disorder.

Indexed as

CopperCorpus StriatumNerve DegenerationParkinson DiseaseSubstantia NigraSuperoxide Dismutase-1AnimalsCoordination ComplexesDietary SupplementsDisease Models, AnimalDopaminergic NeuronsMaleMiceMice, Inbred C57BLMice, TransgenicThiosemicarbazonesCoordination ComplexesCoppercopper (II) diacetyl-di(N(4)-methylthiosemicarbazone)Sod1 protein, mouseSuperoxide Dismutase-1ThiosemicarbazonesCopper supplementationCuATSMMouse modelNeurodegenerationParkinson diseasePost-translational modificationProtein misfoldingSubstantia Nigra Pars compactaSuperoxide dismutase 1

Identifiers

PMID40563111
PMCPMC12188662

What Socratic 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 Socratic graph.