Evidence map›Paper›PMID 24343124›Full record

ArticleMetallomics : integrated biometal science2014

Altered transition metal homeostasis in Niemann-Pick disease, type C1.

Ya Hui Hung, Noel G Faux, David W Killilea, Nicole Yanjanin, Sally Firnkes, Irene Volitakis, George Ganio, Mark Walterfang, Caroline Hastings, Forbes D Porter and 2 more

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

Article in Metallomics : integrated biometal science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

16 citing papers in PubMed, 28 citations in OpenAlex.

  1. Evidence of Oxytosis/Ferroptosis in Niemann-Pick Disease Type C.International journal of molecular sciences · 2025
    Article
  2. Review
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  12. Imaging of changes in copper trafficking and redistribution in a mouse model of Niemann-Pick C disease using positron emission tomography.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2019
    Article
  13. Review
  14. Article
  15. Article
  16. 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

12 authors at 7 institutions in 6 countries.

Ya Hui HungOxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Level 4, Kenneth Myer Building, Parkville, Victoria 3010, Australia. ashley.bush@florey.edu.au.
Noel G Faux
David W Killilea
Nicole Yanjanin
Sally Firnkes
Irene Volitakis
George Ganio
Mark Walterfang
Caroline Hastings
Forbes D Porter
Daniel S Ory
Ashley I Bush
Florey Institute of Neuroscience and Mental Health · AUOakland University · USUniversity of Melbourne · AUWashington University in St. Louis · USBethesda University · USEunice Kennedy Shriver National Institute of Child Health and Human Development · USMoscow Research and Clinical Center for Neuropsychiatry · RU

Funding

Inborn Errors of Cholesterol SynthesisZIAHD000139 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI PORTER, FORBES · 2009 to 2019
$11.7M
Clinical Investigations of Niemann-Pick Disease, type CZIAHD008824 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI PORTER, FORBES · 2009 to 2019
$5.2M
Intramural NIH HHS ZIA HD000139Intramural NIH HHS ZIA HD008824
6 · The paper itself

Abstract

The loss of NPC1 protein function is the predominant cause of Niemann-Pick type C1 disease (NP-C1), a systemic and neurodegenerative disorder characterized by late-endosomal/lysosomal accumulation of cholesterol and other lipids. Limited evidence from post-mortem human tissues, an Npc1(-/-) mouse model, and cell culture studies also suggest failure of metal homeostasis in NP-C1. To investigate these findings, we performed a comprehensive transition metal analysis of cerebrospinal fluid (CSF), plasma and tissue samples from human NP-C1 patients and an Npc1(-/-) mouse model. NPC1 deficiency in the Npc1(-/-) mouse model resulted in a perturbation of transition metal homeostasis in the plasma and key organs (brain, liver, spleen, heart, lungs, and kidneys). Analysis of human patient CSF, plasma and post-mortem brain tissues also indicated disrupted metal homeostasis. There was a disparity in the direction of metal changes between the human and the Npc1(-/-) mouse samples, which may reflect species-specific metal metabolism. Nevertheless, common to both species is brain zinc accumulation. Furthermore, treatment with the glucosylceramide synthase inhibitor miglustat, the only drug shown in a controlled clinical trial to have some efficacy for NP-C1, did not correct the alterations in CSF and plasma transition metal and ceruloplasmin (CP) metabolism in NP-C1 patients. These findings highlight the importance of NPC1 function in metal homeostasis, and indicate that metal-targeting therapy may be of value as a treatment for NP-C.

Indexed as

1-DeoxynojirimycinAnimalsBrainCeruloplasminEnzyme InhibitorsFemaleGene DeletionHomeostasisHumansIntracellular Signaling Peptides and ProteinsMaleMetalsMiceMice, Inbred BALB CNiemann-Pick C1 ProteinNiemann-Pick Disease, Type C1-DeoxynojirimycinCeruloplasminEnzyme InhibitorsIntracellular Signaling Peptides and ProteinsMetalsmiglustatNiemann-Pick C1 ProteinNpc1 protein, mouseProteinsTransition Elements

Identifiers

PMID24343124
PMCPMC4178950
OpenAlexW2043370790

What OpenQuestion holds

Textmetadata
LicenceTDM
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.