Evidence map›Paper›PMID 30897528›Full record

ArticleInternational journal for parasitology. Drugs and drug resistance2019

Histone deacetylase enzymes as potential drug targets of Neglected Tropical Diseases caused by cestodes.

Hugo R Vaca, Ana M Celentano, Natalia Macchiaroli, Laura Kamenetzky, Federico Camicia, Mara C Rosenzvit

Open access · goldAbstract read
In one paragraph

Article in International journal for parasitology. Drugs and drug resistance, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.6field-weighted citation impact, top 12% 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

10 citing papers in PubMed, 22 citations in OpenAlex.

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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

6 authors at 1 institution in 1 country.

Hugo R VacaInstituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Piso 13, Paraguay 2155, CP1121, Buenos Aires, Argentina.
Ana M CelentanoInstituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Piso 13, Paraguay 2155, CP1121, Buenos Aires, Argentina; Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires (UBA), Piso 13, Paraguay 2155, CP1121, Buenos Aires, Argentina.
Natalia MacchiaroliInstituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Piso 13, Paraguay 2155, CP1121, Buenos Aires, Argentina.
Laura KamenetzkyInstituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Piso 13, Paraguay 2155, CP1121, Buenos Aires, Argentina.
Federico CamiciaInstituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Piso 13, Paraguay 2155, CP1121, Buenos Aires, Argentina. Electronic address: fcamicia@fmed.uba.ar.
Mara C RosenzvitInstituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Piso 13, Paraguay 2155, CP1121, Buenos Aires, Argentina. Electronic address: mrosenzvit@fmed.uba.ar.
Consejo Nacional de Investigaciones Científicas y Técnicas · AR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cestode parasites cause neglected diseases, such as echinococcosis and cysticercosis, which represent a significant problem in human and animal health. Benzimidazoles and praziquantel are the only available drugs for chemotherapy and it is therefore important to identify new alternative drugs against cestode parasites. Histone deacetylases (HDACs) are validated drug targets for the treatment of cancer and other diseases, including neglected diseases. However, knowledge of HDACs in cestodes is very scarce. In this work, we investigated cestode HDACs as potential drug targets to develop new therapies against neglected diseases caused by cestodes. Here we showed the full repertoire of HDAC coding genes in several members of the class Cestoda. Between 6 and 7 zinc-dependent HDAC coding genes were identified in the genomes of species from Echinococcus, Taenia, Mesocestoides and Hymenolepis genera. We classified them as Class I and II HDACs and analyzed their transcriptional expression levels throughout developmental stages of Echinococcus spp. We confirmed for the first time the complete HDAC8 nucleotide sequences from Echinococcus canadensis G7 and Mesocestoides corti. Homology models for these proteins showed particular structural features which differentiate them from HDAC8 from Homo sapiens. Furthermore, we showed that Trichostatin A (TSA), a pan-HDAC inhibitor, decreases the viability of M. corti, alters its tegument and morphology and produces an increment of the total amount of acetylated proteins, including acetylated histone H4. These results suggest that HDAC from cestodes are functional and might play important roles on survival and development. The particular structural features observed in cestode HDAC8 proteins suggest that these enzymes could be selectively targeted. This report provides the basis for further studies on cestode HDAC enzymes and for discovery of new HDAC inhibitors for the treatment of neglected diseases caused by cestode parasites.

Indexed as

AnimalsCestodaCestode InfectionsFemaleHistone Deacetylase InhibitorsHistone DeacetylasesHistonesHydroxamic AcidsMiceMice, Inbred BALB CNeglected DiseasesRatsRats, WistarHistone Deacetylase InhibitorsHistone DeacetylasesHistonesHydroxamic Acidstrichostatin ACestodeEchinococcusHistone deacetylasesMesocestoides cortiNeglected Tropical DiseasesTrichostatin A

Identifiers

PMID30897528
PMCPMC6426703
OpenAlexW2917622654

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.