Evidence map›Paper›PMID 37174628›Full record

ArticleCells2023

Integrated Omic Analysis Delineates Pathways Modulating Toxic TDP-43 Protein Aggregates in Amyotrophic Lateral Sclerosis.

Saiswaroop Rajaratnam, Akhil P Soman, Kanikaram Sai Phalguna, Sai Sanwid Pradhan, Meghana Manjunath, Raksha Kanthavara Rao, Rajesh Babu Dandamudi, Sai Krishna Srimadh Bhagavatham, Sujith Kumar Pulukool, Sriram Rathnakumar and 7 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 7% 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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Genetic associations with dementia-related proteinopathy: Application of item response theory.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  7. International journal of molecular sciences · 2023
    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

17 authors at 7 institutions in 3 countries.

Saiswaroop RajaratnamDisease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Anantapur 515134, Andhra Pradesh, India.ORCID 0000-0001-7163-5263
Akhil P SomanDisease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Anantapur 515134, Andhra Pradesh, India.
Kanikaram Sai PhalgunaDisease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Anantapur 515134, Andhra Pradesh, India.ORCID 0000-0001-8972-7983
Sai Sanwid PradhanDisease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Anantapur 515134, Andhra Pradesh, India.ORCID 0000-0002-5461-8047
Meghana ManjunathInstitute of Bioinformatics and Applied Biotechnology, Bengaluru 560100, Karnataka, India.
Raksha Kanthavara RaoInstitute of Bioinformatics and Applied Biotechnology, Bengaluru 560100, Karnataka, India.
Rajesh Babu DandamudiPhenomenex India, Hyderabad 500084, Telangana, India.
Sai Krishna Srimadh BhagavathamDisease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Anantapur 515134, Andhra Pradesh, India.
Sujith Kumar PulukoolDisease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Anantapur 515134, Andhra Pradesh, India.
Sriram RathnakumarDisease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Anantapur 515134, Andhra Pradesh, India.
Sai KocherlakotaLaboratory of Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium.ORCID 0000-0002-2488-2832
Ashish PargaonkarApplication Division, Agilent Technologies Ltd., Bengaluru 560066, Karnataka, India.
Ravindra P VeerannaDepartment of Biochemistry, Council of Scientific & Industrial Research (CSIR)-Central Food Technological Research Institute (CFTRI), Mysuru 570020, Karnataka, India.ORCID 0000-0003-4228-1843
Natarajan ArumugamDepartment of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.ORCID 0000-0001-9073-155X
Abdulrahman I AlmansourDepartment of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Bibha ChoudharyInstitute of Bioinformatics and Applied Biotechnology, Bengaluru 560100, Karnataka, India.
Venketesh SivaramakrishnanDisease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Anantapur 515134, Andhra Pradesh, India.ORCID 0000-0003-3094-5905
Sri Sathya Sai Institute of Higher Learning · INInstitute of Bioinformatics and Applied Biotechnology · INKing Saud University · SAAgilent Technologies (India) · INCentral Food Technological Research Institute · INCentral Water and Power Research Station · INKU Leuven · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Amyotrophic lateral sclerosis (ALS) is a multi-systemic, incurable, amyloid disease affecting the motor neurons, resulting in the death of patients. The disease is either sporadic or familial with SOD1, C9orf72, FUS, and TDP-43 constituting the majority of familial ALS. Multi-omics studies on patients and model systems like mice and yeast have helped in understanding the association of various signaling and metabolic pathways with the disease. The yeast model system has played a pivotal role in elucidating the gene amyloid interactions. We carried out an integrated transcriptomic and metabolomic analysis of the TDP-43 expressing yeast model to elucidate deregulated pathways associated with the disease. The analysis shows the deregulation of the TCA cycle, single carbon metabolism, glutathione metabolism, and fatty acid metabolism. Transcriptomic analysis of GEO datasets of TDP-43 expressing motor neurons from mice models of ALS and ALS patients shows considerable overlap with experimental results. Furthermore, a yeast model was used to validate the obtained results using metabolite addition and gene knock-out experiments. Taken together, our result shows a potential role for the TCA cycle, cellular redox pathway, NAD metabolism, and fatty acid metabolism in disease. Supplementation of reduced glutathione, nicotinate, and the keto diet might help to manage the disease.

Indexed as

Amyotrophic Lateral SclerosisAnimalsDNA-Binding ProteinsFatty AcidsMiceProtein AggregatesSaccharomyces cerevisiaeDNA-Binding ProteinsFatty AcidsProtein AggregatesTardbp protein, mouseALSmetabolomicsneurodegenerative diseaseprotein aggregatestranscriptomics

Identifiers

PMID37174628
PMCPMC10177613
OpenAlexW4366828806

What OpenQuestion 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 OpenQuestion graph.