Evidence map›Paper›PMID 38412549›Full record

ArticleG3 (Bethesda, Md.)2024

Ribonucleotide reductase inhibition improves the symptoms of a Caenorhabditis elegans model of Alzheimer's disease.

Ana M Brokate-Llanos, Mireya Sanchez-Ibañez, Mercedes M Pérez-Jiménez, José M Monje-Moreno, Carlos Gómez-Marín, Carlos Caro, Carlos Vivar-Rios, Miguel A Moreno-Mateos, María L García-Martín, Manuel J Muñoz and 1 more

Open access · goldAbstract read
In one paragraph

Article in G3 (Bethesda, Md.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 52% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. 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

11 authors at 3 institutions in 1 country.

Ana M Brokate-LlanosCentro Andaluz de Biologia del Desarrollo, University Pablo de Olavide-CISC-Junta de Andalucía, Ctra Utrera Km 1, Sevilla 41013, Spain.
Mireya Sanchez-IbañezDepartment of Surgery, Immunology and Biochemistry, School of Medicine, University of Malaga, Boulevar Louis Pasteur s/n, Málaga 29010, Spain.
Mercedes M Pérez-JiménezCentro Andaluz de Biologia del Desarrollo, University Pablo de Olavide-CISC-Junta de Andalucía, Ctra Utrera Km 1, Sevilla 41013, Spain.
José M Monje-MorenoCentro Andaluz de Biologia del Desarrollo, University Pablo de Olavide-CISC-Junta de Andalucía, Ctra Utrera Km 1, Sevilla 41013, Spain.
Carlos Gómez-MarínCentro Andaluz de Biologia del Desarrollo, University Pablo de Olavide-CISC-Junta de Andalucía, Ctra Utrera Km 1, Sevilla 41013, Spain.
Carlos CaroAndalusian Centre for Nanomedicine and Biotechnology (Junta de Andalucía-Universidad de Málaga), BIONAND, Málaga 29590, Spain.
Carlos Vivar-RiosDepartment of Surgery, Immunology and Biochemistry, School of Medicine, University of Malaga, Boulevar Louis Pasteur s/n, Málaga 29010, Spain.
Miguel A Moreno-MateosCentro Andaluz de Biologia del Desarrollo, University Pablo de Olavide-CISC-Junta de Andalucía, Ctra Utrera Km 1, Sevilla 41013, Spain.
María L García-MartínAndalusian Centre for Nanomedicine and Biotechnology (Junta de Andalucía-Universidad de Málaga), BIONAND, Málaga 29590, Spain.
Manuel J MuñozCentro Andaluz de Biologia del Desarrollo, University Pablo de Olavide-CISC-Junta de Andalucía, Ctra Utrera Km 1, Sevilla 41013, Spain.ORCID 0000-0002-0111-1541
José L RoyoDepartment of Surgery, Immunology and Biochemistry, School of Medicine, University of Malaga, Boulevar Louis Pasteur s/n, Málaga 29010, Spain.
Centro Andaluz de Biología del Desarrollo · ESUniversidad de Málaga · ESAndalusian Centre for Nanomedicine and Biotechnology · ES

Funding

Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Aric L Daul, Ann E. Rougvie · 2012 to 2026
$7.5M
NIH HHS P40 OD010440
6 · The paper itself

Abstract

Alzheimer's disease is the main cause of aging-associated dementia, for which there is no effective treatment. In this work, we reanalyze the information of a previous genome wide association study, using a new pipeline design to identify novel potential drugs. With this approach, ribonucleoside-diphosphate reductase gene (RRM2B) emerged as a candidate target and its inhibitor, 2', 2'-difluoro 2'deoxycytidine (gemcitabine), as a potential pharmaceutical drug against Alzheimer's disease. We functionally verified the effect of inhibiting the RRM2B homolog, rnr-2, in an Alzheimer's model of Caenorhabditis elegans, which accumulates human Aβ1-42 peptide to an irreversible paralysis. RNA interference against rnr-2 and also treatment with 200 ng/ml of gemcitabine, showed an improvement of the phenotype. Gemcitabine treatment increased the intracellular ATP level 3.03 times, which may point to its mechanism of action. Gemcitabine has been extensively used in humans for cancer treatment but at higher concentrations. The 200 ng/ml concentration did not exert a significant effect over cell cycle, or affected cell viability when assayed in the microglia N13 cell line. Thus, the inhibitory drug of the RRM2B activity could be of potential use to treat Alzheimer's disease and particularly gemcitabine might be considered as a promising candidate to be repurposed for its treatment.

Indexed as

Alzheimer DiseaseCaenorhabditis elegansDeoxycytidineDisease Models, AnimalAdenosine TriphosphateAmyloid beta-PeptidesAnimalsCaenorhabditis elegans ProteinsEnzyme InhibitorsGemcitabineHumansRibonucleoside Diphosphate ReductaseRibonucleotide ReductasesRNA InterferenceAdenosine TriphosphateAmyloid beta-PeptidesCaenorhabditis elegans ProteinsDeoxycytidineEnzyme InhibitorsGemcitabineRibonucleoside Diphosphate ReductaseRibonucleotide ReductasesAlzheimerCaenorhabditis elegansgemcitabineRRM2B

Identifiers

PMID38412549
PMCPMC11075554
OpenAlexW4392185149

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.