Evidence map›Paper›PMID 26698023›Full record

ReviewNature reviews. Rheumatology2016

Activation of mTOR (mechanistic target of rapamycin) in rheumatic diseases.

Andras Perl

Open access · greenAbstract readReview
In one paragraph

Review in Nature reviews. Rheumatology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 190 papers.

0numbers the graph read from it
0cells of the map it votes in
190citing papers in PubMed
11.4field-weighted citation impact, top 1% 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

190 citing papers in PubMed, 315 citations in OpenAlex.

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130 more citing papers are in PubMed but not listed here.

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

1 author at 1 institution in 1 country.

Andras PerlDivision of Rheumatology, Departments of Medicine, Microbiology and Immunology, and Biochemistry and Molecular Biology, State University of New York, Upstate Medical University, College of Medicine, 750 East Adams Street, Syracuse, New York 13210, USA.
SUNY Upstate Medical University · US

Funding

Metabolic Control of T-cell Lineage Specification in SLER01AI072648 · NIAID · UPSTATE MEDICAL UNIVERSITY · PI PERL, ANDRAS · 2008 to 2024
$6.1M
IMPACT OF HRES-1 ENDOGENOUS RETROVIRUS IN SLER01AI048079 · NIAID · UPSTATE MEDICAL UNIVERSITY · PI PERL, ANDRAS · 2000 to 2013
$2.7M
Endocytic Control of Autophagosome Formation in Lupus T cellsR01AI122176 · NIAID · UPSTATE MEDICAL UNIVERSITY · PI PERL, ANDRAS · 2016 to 2020
$2.0M
Treatment of SLE with N-acetylcysteineR01AT004332 · NCCIH · UPSTATE MEDICAL UNIVERSITY · PI PERL, ANDRAS · 2008 to 2011
$1.6M
Pathogenesis and Treatment of Liver Disease in Transaldolase DeficiencyR01DK078922 · NIDDK · UPSTATE MEDICAL UNIVERSITY · PI PERL, ANDRAS · 2010 to 2013
$1.4M
MOLECULAR BIOLOGY OF TRANSALDOLASER01DK049221 · NIDDK · UPSTATE MEDICAL UNIVERSITY · PI PERL, ANDRAS · 1996 to 2004
$904k
Treatment of Systemic Lupus Erythematosus (SLE) with N-acetylcysteine (NAC)R34AR068052 · NIAMS · UPSTATE MEDICAL UNIVERSITY · PI MCDERMOTT, MICHAEL P, PERL, ANDRAS · 2016 to 2017
$405k
Genetic and Immunological Impact of the HRES-1/Rab4 Locus in SLER56AI048079 · NIAID · UPSTATE MEDICAL UNIVERSITY · PI PERL, ANDRAS · 2008 to 2008
$275k
Mitochondrial dysfunction in patients with SLER21AI061066 · NIAID · UPSTATE MEDICAL UNIVERSITY · PI PERL, ANDRAS · 2004 to 2004
$266k
NCCIH NIH HHS R01 AT004332NIAID NIH HHS AI 048079NIAID NIH HHS AI 072648NIAID NIH HHS R01 AI048079NIAID NIH HHS R01 AI072648NIAID NIH HHS R01 AI122176NIAID NIH HHS R21 AI061066NIAID NIH HHS R56 AI048079NIAMS NIH HHS R34 AR068052NIDDK NIH HHS R01 DK049221NIDDK NIH HHS R01 DK078922
6 · The paper itself

Abstract

Mechanistic target of rapamycin (mTOR, also known as mammalian target of rapamycin) is a ubiquitous serine/threonine kinase that regulates cell growth, proliferation and survival. These effects are cell-type-specific, and are elicited in response to stimulation by growth factors, hormones and cytokines, as well as to internal and external metabolic cues. Rapamycin was initially developed as an inhibitor of T-cell proliferation and allograft rejection in the organ transplant setting. Subsequently, its molecular target (mTOR) was identified as a component of two interacting complexes, mTORC1 and mTORC2, that regulate T-cell lineage specification and macrophage differentiation. mTORC1 drives the proinflammatory expansion of T helper (TH) type 1, TH17, and CD4(-)CD8(-) (double-negative, DN) T cells. Both mTORC1 and mTORC2 inhibit the development of CD4(+)CD25(+)FoxP3(+) T regulatory (TREG) cells and, indirectly, mTORC2 favours the expansion of T follicular helper (TFH) cells which, similarly to DN T cells, promote B-cell activation and autoantibody production. In contrast to this proinflammatory effect of mTORC2, mTORC1 favours, to some extent, an anti-inflammatory macrophage polarization that is protective against infections and tissue inflammation. Outside the immune system, mTORC1 controls fibroblast proliferation and chondrocyte survival, with implications for tissue fibrosis and osteoarthritis, respectively. Rapamycin (which primarily inhibits mTORC1), ATP-competitive, dual mTORC1/mTORC2 inhibitors and upstream regulators of the mTOR pathway are being developed to treat autoimmune, hyperproliferative and degenerative diseases. In this regard, mTOR blockade promises to increase life expectancy through treatment and prevention of rheumatic diseases.

Indexed as

AnimalsEnzyme ActivationHumansProtein Kinase InhibitorsRheumatic DiseasesTOR Serine-Threonine KinasesProtein Kinase InhibitorsTOR Serine-Threonine Kinases

Identifiers

PMID26698023
PMCPMC5314913
OpenAlexW2238610105

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.