Evidence map›Paper›PMID 29142509›Full record

ArticleMetabolomics : Official journal of the Metabolomic Society2017

Using an NMR metabolomics approach to investigate the pathogenicity of amyloid-beta and alpha-synuclein.

M M Phelan, E Caamaño-Gutiérrez, M S Gant, R X Grosman, J Madine

Abstract read
In one paragraph

Article in Metabolomics : Official journal of the Metabolomic Society, 2017. 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
–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

16 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Chemical catalysis by biological amyloids.Biochemical Society transactions · 2023
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. The Diagnostic Potential of Amyloidogenic Proteins.International journal of molecular sciences · 2021
    Review
  13. Article
  14. Review
  15. A new era for understanding amyloid structures and disease.Nature reviews. Molecular cell biology · 2018
    Review
  16. 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

5 authors.

M M PhelanInstitute of Integrative Biology, University of Liverpool, Liverpool, UK.
E Caamaño-GutiérrezInstitute of Integrative Biology, University of Liverpool, Liverpool, UK.
M S GantInstitute of Integrative Biology, University of Liverpool, Liverpool, UK.
R X GrosmanInstitute of Integrative Biology, University of Liverpool, Liverpool, UK.
J MadineInstitute of Integrative Biology, University of Liverpool, Liverpool, UK.ORCID 0000-0001-9963-5871

Funding

Medical Research Council MR/M009114/1
6 · The paper itself

Abstract

introductionThe pathogenicity at differing points along the aggregation pathway of many fibril-forming proteins associated with neurodegenerative diseases is unclear. Understanding the effect of different aggregation states of these proteins on cellular processes is essential to enhance understanding of diseases and provide future options for diagnosis and therapeutic intervention.

objectivesTo establish a robust method to probe the metabolic changes of neuronal cells and use it to monitor cellular response to challenge with three amyloidogenic proteins associated with neurodegenerative diseases in different aggregation states.

methodNeuroblastoma SH-SY5Y cells were employed to design a robust routine system to perform a statistically rigorous NMR metabolomics study into cellular effects of sub-toxic levels of alpha-synuclein, amyloid-beta 40 and amyloid-beta 42 in monomeric, oligomeric and fibrillar conformations.

resultsThis investigation developed a rigorous model to monitor intracellular metabolic profiles of neuronal cells through combination of existing methods. This model revealed eight key metabolites that are altered when neuroblastoma cells are challenged with proteins in different aggregation states. Metabolic pathways associated with lipid metabolism, neurotransmission and adaptation to oxidative stress and inflammation are the predominant contributors to the cellular variance and intracellular metabolite levels. The observed metabolite changes for monomer and oligomer challenge may represent cellular effort to counteract the pathogenicity of the challenge, whereas fibrillar challenge is indicative of system shutdown. This implies that although markers of stress are more prevalent under oligomeric challenge the fibrillar response suggests a more toxic environment.

conclusionThis approach is applicable to any cell type that can be cultured in a laboratory (primary or cell line) as a method of investigating how protein challenge affects signalling pathways, providing additional understanding as to the role of protein aggregation in neurodegenerative disease initiation and progression.

Indexed as

Alpha-synucleinAlzheimer’s diseaseAmyloid-betaMetabolomicsNMR spectroscopyParkinson’s disease

Identifiers

PMID29142509
PMCPMC5661010

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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.