Evidence map›Paper›PMID 33761951›Full record

ArticleBMC biology2021

Neuronal cell-based high-throughput screen for enhancers of mitochondrial function reveals luteolin as a modulator of mitochondria-endoplasmic reticulum coupling.

Luana Naia, Catarina M Pinho, Giacomo Dentoni, Jianping Liu, Nuno Santos Leal, Duarte M S Ferreira, Bernadette Schreiner, Riccardo Filadi, Lígia Fão, Niamh M C Connolly and 17 more

Open access · goldAbstract read
In one paragraph

Article in BMC biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

24 citing papers in PubMed, 35 citations in OpenAlex.

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  19. Flavonoids-Natural Gifts to Promote Health and Longevity.International journal of molecular sciences · 2022
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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

27 authors at 7 institutions in 6 countries.

Luana Naia *Center for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Catarina M Pinho *Center for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Giacomo DentoniCenter for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Jianping LiuDepartment of Medicine-Huddinge, Karolinska Institutet, Stockholm, Sweden.
Nuno Santos LealCenter for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Duarte M S FerreiraDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Bernadette SchreinerCenter for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Riccardo FiladiDepartment of Biomedical Sciences, University of Padua, Padua, Italy.
Lígia FãoCNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Niamh M C ConnollyRoyal College of Surgeons in Ireland, Department of Physiology & Medical Physics Department, Dublin, Ireland.
Pontus ForsellAlzeCure Pharma AB, Huddinge, Sweden.
Gunnar NordvallAlzeCure Pharma AB, Huddinge, Sweden.
Makoto ShimozawaCenter for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Elisa GreottiDepartment of Biomedical Sciences, University of Padua, Padua, Italy.
Emy BassoDepartment of Biomedical Sciences, University of Padua, Padua, Italy.
Pierre TheureyDepartment of Biomedical Sciences, University of Padua, Padua, Italy.
Anna GioranGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Alvin JoselinDepartment of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Marie Arsenian-HenrikssonDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Per NilssonCenter for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
A Cristina RegoCNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Jorge L RuasDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
David ParkDepartment of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Daniele BanoGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Paola PizzoDepartment of Biomedical Sciences, University of Padua, Padua, Italy.
Jochen H M PrehnRoyal College of Surgeons in Ireland, Department of Physiology & Medical Physics Department, Dublin, Ireland.
Maria AnkarcronaCenter for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden. maria.ankarcrona@ki.se.ORCID 0000-0002-7022-3694
Karolinska Institutet · SEUniversity of Padua · ITAlzeCure Pharma (Sweden) · SEGerman Center for Neurodegenerative Diseases · DERoyal College of Surgeons in Ireland · IEUniversity of Calgary · CAUniversity of Coimbra · PT

Funding

Joint Programme in Neurodegenerative Disorders JPND_CD_FP-688-025
6 · The paper itself

Abstract

backgroundMitochondrial dysfunction is a common feature of aging, neurodegeneration, and metabolic diseases. Hence, mitotherapeutics may be valuable disease modifiers for a large number of conditions. In this study, we have set up a large-scale screening platform for mitochondrial-based modulators with promising therapeutic potential.

resultsUsing differentiated human neuroblastoma cells, we screened 1200 FDA-approved compounds and identified 61 molecules that significantly increased cellular ATP without any cytotoxic effect. Following dose response curve-dependent selection, we identified the flavonoid luteolin as a primary hit. Further validation in neuronal models indicated that luteolin increased mitochondrial respiration in primary neurons, despite not affecting mitochondrial mass, structure, or mitochondria-derived reactive oxygen species. However, we found that luteolin increased contacts between mitochondria and endoplasmic reticulum (ER), contributing to increased mitochondrial calcium (Ca

conclusionWe provide a new screening platform for drug discovery validated in vitro and ex vivo. In addition, we describe a novel mechanism through which luteolin modulates mitochondrial activity in neuronal models with potential therapeutic validity for treatment of a variety of human diseases.

Indexed as

AnimalsCell Line, TumorDrug Evaluation, PreclinicalEndoplasmic ReticulumHigh-Throughput Screening AssaysHumansLuteolinMiceMitochondriaNeuronsSignal TransductionLuteolinHigh-throughput screenLuteolinMitochondriaMitochondria-ER contactsMitochondrial calcium

Identifiers

PMID33761951
PMCPMC7989211
OpenAlexW3137453670

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.