Evidence map›Paper›PMID 24355812›Full record

ReviewThe international journal of biochemistry & cell biology2014

α1-antitrypsin deficiency and the hepatocytes - an elegans solution to drug discovery.

Linda P O'Reilly, David H Perlmutter, Gary A Silverman, Stephen C Pak

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in The international journal of biochemistry & cell biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact, top 91% 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

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Impact of drug solvents onToxicology reports · 2021
    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

4 authors at 2 institutions in 1 country.

Linda P O'ReillyDepartment of Pediatrics, Cell Biology and Physiology, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
David H PerlmutterDepartment of Pediatrics, Cell Biology and Physiology, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
Gary A SilvermanDepartment of Pediatrics, Cell Biology and Physiology, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
Stephen C PakDepartment of Pediatrics, Cell Biology and Physiology, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA. Electronic address: stephen.pak@chp.edu.
Children's Hospital of Pittsburgh · USUniversity of Pittsburgh · US

Funding

Treating AT Deficiency with Drugs that Modulate the Proteostasis NetworkP01DK096990 · NIDDK · WASHINGTON UNIVERSITY · PI SILVERMAN, GARY ARTHUR · 2012 to 2023
$18.3M
Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Aric L Daul, Ann E. Rougvie · 2012 to 2026
$7.5M
High Throughput Genetic and Drug Screens for Alph-1-Antitrypsin DeficiencyR01DK079806 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SILVERMAN, GARY ARTHUR · 2008 to 2011
$2.4M
Intracellular Serpin Regulation of Intestinal Cell NecrosisR01DK081422 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SILVERMAN, GARY ARTHUR · 2009 to 2012
$1.6M
Novel Pharmacological Strategies for Liver Disease in Antitrypsin DeficiencyR01DK084512 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PERLMUTTER, DAVID H · 2009 to 2012
$1.6M
NIDDK NIH HHS DK079806NIDDK NIH HHS DK081422NIDDK NIH HHS DK084512NIDDK NIH HHS DK096990NIDDK NIH HHS P01 DK096990NIDDK NIH HHS R01 DK079806NIDDK NIH HHS R01 DK081422NIDDK NIH HHS R01 DK084512NIH HHS P40 OD010440
6 · The paper itself

Abstract

Hepatocytes are metabolically active cells of the liver that play an important role in the biosynthesis of proteins including α1-antitrypsin. Mutations in the α1-antitrypsin gene can lead to protein misfolding, polymerization/aggregation and retention of protein within the endoplasmic reticulum of hepatocytes. The intracellular accumulation of α1-antitrypsin aggregates can lead to liver disease and increased likelihood of developing hepatocellular carcinomas. Of note, only ~10% of individuals with α1-antitrypsin-deficiency develop severe liver disease suggesting that there are other genetic and/or environmental factors that determine disease outcome. The nematode, Caenorhabditis elegans, is a powerful genetic model organism to study molecular aspects of human disease. In this review, we discuss the functional similarities between the intestinal cells of C. elegans and human hepatocytes and how a C. elegans model of α1-antitrypsin-deficiency can be used as a tool for identifying genetic modifiers and small molecule drugs.

Indexed as

Caenorhabditis elegansDisease Models, Animalalpha 1-Antitrypsin DeficiencyAnimalsDrug DiscoveryHepatocytesHumansC. elegansHepatocyteLiver diseaseProtein aggregationα1-Antitrypsin deficiency

Identifiers

PMID24355812
PMCPMC3970812
OpenAlexW1993997684

What OpenQuestion holds

Textmetadata
LicenceTDM
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.