Evidence map›Paper›PMID 29531801›Full record

ArticleCell death discovery2018

Inhibition of the MID1 protein complex: a novel approach targeting APP protein synthesis.

Frank Matthes, Moritz M Hettich, Judith Schilling, Diana Flores-Dominguez, Nelli Blank, Thomas Wiglenda, Alexander Buntru, Hanna Wolf, Stephanie Weber, Ina Vorberg and 5 more

Open access · goldAbstract read
In one paragraph

Article in Cell death discovery, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

23 citing papers in PubMed, 58 citations in OpenAlex.

  1. Targeting the cGAS-STING pathway mitigates Huntington disease pathogenesis in a knock-in mouse model.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  15. TRIM18-Regulated STAT3 Signaling PathwayFrontiers in physiology · 2021
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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

15 authors at 2 institutions in 2 countries.

Frank Matthes *1Deutsches Zentrum für Neurodegenerative Erkrankungen e.V., Bonn, Germany.
Moritz M Hettich *1Deutsches Zentrum für Neurodegenerative Erkrankungen e.V., Bonn, Germany.
Judith Schilling *1Deutsches Zentrum für Neurodegenerative Erkrankungen e.V., Bonn, Germany.
Diana Flores-Dominguez1Deutsches Zentrum für Neurodegenerative Erkrankungen e.V., Bonn, Germany.
Nelli Blank1Deutsches Zentrum für Neurodegenerative Erkrankungen e.V., Bonn, Germany.
Thomas Wiglenda2Max Delbrueck Center for Molecular Medicine (MDC) Berlin-Buch, Berlin, Germany.
Alexander Buntru2Max Delbrueck Center for Molecular Medicine (MDC) Berlin-Buch, Berlin, Germany.
Hanna Wolf1Deutsches Zentrum für Neurodegenerative Erkrankungen e.V., Bonn, Germany.
Stephanie Weber1Deutsches Zentrum für Neurodegenerative Erkrankungen e.V., Bonn, Germany.
Ina Vorberg1Deutsches Zentrum für Neurodegenerative Erkrankungen e.V., Bonn, Germany.ORCID 0000-0003-0583-4015
Alina Dagane2Max Delbrueck Center for Molecular Medicine (MDC) Berlin-Buch, Berlin, Germany.
Gunnar Dittmar2Max Delbrueck Center for Molecular Medicine (MDC) Berlin-Buch, Berlin, Germany.
Erich Wanker2Max Delbrueck Center for Molecular Medicine (MDC) Berlin-Buch, Berlin, Germany.
Dan Ehninger1Deutsches Zentrum für Neurodegenerative Erkrankungen e.V., Bonn, Germany.
Sybille Krauss1Deutsches Zentrum für Neurodegenerative Erkrankungen e.V., Bonn, Germany.
German Center for Neurodegenerative Diseases · DEMax Delbrück Center · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer's disease (AD) is characterized by two neuropathological hallmarks: senile plaques, which are composed of amyloid-β (Aβ) peptides, and neurofibrillary tangles, which are composed of hyperphosphorylated tau protein. Aβ peptides are derived from sequential proteolytic cleavage of the amyloid precursor protein (APP). In this study, we identified a so far unknown mode of regulation of APP protein synthesis involving the MID1 protein complex: MID1 binds to and regulates the translation of APP mRNA. The underlying mode of action of MID1 involves the mTOR pathway. Thus, inhibition of the MID1 complex reduces the APP protein level in cultures of primary neurons. Based on this, we used one compound that we discovered previously to interfere with the MID1 complex, metformin, for in vivo experiments. Indeed, long-term treatment with metformin decreased APP protein expression levels and consequently Aβ in an AD mouse model. Importantly, we have initiated the metformin treatment late in life, at a time-point where mice were in an already progressed state of the disease, and could observe an improved behavioral phenotype. These findings together with our previous observation, showing that inhibition of the MID1 complex by metformin also decreases tau phosphorylation, make the MID1 complex a particularly interesting drug target for treating AD.

Identifiers

PMID29531801
PMCPMC5841321
OpenAlexW2789352630

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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.