Evidence map›Paper›PMID 35897651›Full record

ReviewInternational journal of molecular sciences2022

The mTOR Signaling Pathway in Multiple Sclerosis; from Animal Models to Human Data.

Aigli G Vakrakou, Anastasia Alexaki, Maria-Evgenia Brinia, Maria Anagnostouli, Leonidas Stefanis, Panos Stathopoulos

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 2 pooled it
7.2field-weighted citation impact, top 2% 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

34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.

  1. Pooled it
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  13. mTOR Signaling in Macrophages: All Depends on the Context.International journal of molecular sciences · 2025
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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.

Aigli G VakrakouFirst Department of Neurology, Medical School, National and Kapodistrian University of Athens, V Sofias 72, 11528 Athens, Greece.
Anastasia AlexakiFirst Department of Neurology, Medical School, National and Kapodistrian University of Athens, V Sofias 72, 11528 Athens, Greece.
Maria-Evgenia BriniaFirst Department of Neurology, Medical School, National and Kapodistrian University of Athens, V Sofias 72, 11528 Athens, Greece.
Maria AnagnostouliFirst Department of Neurology, Medical School, National and Kapodistrian University of Athens, V Sofias 72, 11528 Athens, Greece.ORCID 0000-0001-8934-670X
Leonidas StefanisFirst Department of Neurology, Medical School, National and Kapodistrian University of Athens, V Sofias 72, 11528 Athens, Greece.
Panos StathopoulosFirst Department of Neurology, Medical School, National and Kapodistrian University of Athens, V Sofias 72, 11528 Athens, Greece.
National and Kapodistrian University of Athens · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This article recapitulates the evidence on the role of mammalian targets of rapamycin (mTOR) complex pathways in multiple sclerosis (MS). Key biological processes that intersect with mTOR signaling cascades include autophagy, inflammasome activation, innate (e.g., microglial) and adaptive (B and T cell) immune responses, and axonal and neuronal toxicity/degeneration. There is robust evidence that mTOR inhibitors, such as rapamycin, ameliorate the clinical course of the animal model of MS, experimental autoimmune encephalomyelitis (EAE). New, evolving data unravel mechanisms underlying the therapeutic effect on EAE, which include balance among T-effector and T-regulatory cells, and mTOR effects on myeloid cell function, polarization, and antigen presentation, with relevance to MS pathogenesis. Radiologic and preliminary clinical data from a phase 2 randomized, controlled trial of temsirolimus (a rapamycin analogue) in MS show moderate efficacy, with significant adverse effects. Large clinical trials of indirect mTOR inhibitors (metformin) in MS are lacking; however, a smaller prospective, non-randomized study shows some potentially promising radiological results in combination with ex vivo beneficial effects on immune cells that might warrant further investigation. Importantly, the study of mTOR pathway contributions to autoimmune inflammatory demyelination and multiple sclerosis illustrates the difficulties in the clinical application of animal model results. Nevertheless, it is not inconceivable that targeting metabolism in the future with cell-selective mTOR inhibitors (compared to the broad inhibitors tried to date) could be developed to improve efficacy and reduce side effects.

Indexed as

Encephalomyelitis, Autoimmune, ExperimentalMultiple SclerosisTOR Serine-Threonine KinasesAnimalsClinical Trials, Phase II as TopicDisease Models, AnimalHumansMiceMice, Inbred C57BLProspective StudiesRandomized Controlled Trials as TopicSignal TransductionSirolimusMTOR protein, humanSirolimusTOR Serine-Threonine KinasesmetforminmTORmultiple sclerosisrapamycin

Identifiers

PMID35897651
PMCPMC9332053
OpenAlexW4286586441

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.