Evidence map›Paper›PMID 36373957›Full record

ArticleAging cell2022

4-phenylbutyric acid-Identity crisis; can it act as a translation inhibitor?

Daniel Stein, Zeev Slobodnik, Benjamin Tam, Monica Einav, Barak Akabayov, Shimon Berstein, Debra Toiber

Open access · goldAbstract read
In one paragraph

Article in Aging cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

  1. [Protective effect of the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid against myocardial injury in septic mice].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026
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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

7 authors at 1 institution in 1 country.

Daniel SteinDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Zeev SlobodnikDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Benjamin TamDepartment of Chemistry, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Monica EinavDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Barak AkabayovDepartment of Chemistry, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Shimon BersteinDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Debra ToiberDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.ORCID https://orcid.org/0000-0002-1465-0130
Ben-Gurion University of the Negev · IL

Funding

Bio-tech and Negev fellowships of Kreitman School of Advanced Research of Ben Gurion UniversityDavid and Inez Myers Foundation
6 · The paper itself

Abstract

Loss of proteostasis can occur due to mutations, the formation of aggregates, or general deficiency in the correct translation and folding of proteins. These phenomena are commonly observed in pathologies, but most significantly, loss of proteostasis characterizes aging. This loss leads to the chronic activation of stress responses and has a generally deleterious impact on the organism. While finding molecules that can alleviate these symptoms is an important step toward solutions for these conditions, some molecules might be mischaracterized on the way. 4-phenylbutyric acid (4PBA) is known for its role as a chemical chaperone that helps alleviate endoplasmic reticulum (ER) stress, yet a scan of the literature reveals that no biochemical or molecular experiments have shown any protein refolding capacity. Here, we show that 4PBA is a conserved weak inhibitor of mRNA translation, both in vitro and in cellular systems, and furthermore-it does not promote protein folding nor prevents aggregation. 4PBA possibly alleviates proteostatic or ER stress by inhibiting protein synthesis, allowing the cells to cope with misfolded proteins by reducing the protein load. Better understanding of 4PBA biochemical mechanisms will improve its usage in basic science and as a drug in different pathologies, also opening new venues for the treatment of different diseases.

Indexed as

Endoplasmic Reticulum StressPhenylbutyratesProtein FoldingProteostasisUnfolded Protein Response4-phenylbutyric acidPhenylbutyrates4PBAchemical chaperoneprotein synthesisProteostasistranslation inhibitionunfolded protein response

Identifiers

PMID36373957
PMCPMC9741500
OpenAlexW4308952041

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.