Evidence map›Paper›PMID 24770416›Full record

ArticleThe Journal of biological chemistry2014

The phytoestrogen genistein modulates lysosomal metabolism and transcription factor EB (TFEB) activation.

Marta Moskot, Sandro Montefusco, Joanna Jakóbkiewicz-Banecka, Paweł Mozolewski, Alicja Węgrzyn, Diego Di Bernardo, Grzegorz Węgrzyn, Diego L Medina, Andrea Ballabio, Magdalena Gabig-Cimińska

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 1 pooled it
7.5field-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

81 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.

  1. Guideline
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  4. Advances in Therapies for Mucopolysaccharidoses.Current issues in molecular biology · 2026
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21 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

10 authors at 5 institutions in 3 countries.

Marta MoskotFrom the Laboratory of Molecular Biology (affiliated with the University of Gdańsk), Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Wita Stwosza 59, 80-308 Gdańsk, Poland.
Sandro Montefuscothe High Content Screening Facility, Telethon Institute of Genetics and Medicine (TIGEM), Via P. Castellino 111, 80131 Naples, Italy.
Joanna Jakóbkiewicz-Baneckathe Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
Paweł Mozolewskithe Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
Alicja Węgrzynthe Department of Microbiology, University of Szczecin, Felczaka 3c, 71-412 Szczecin, Szczecin, Poland.
Diego Di Bernardothe High Content Screening Facility, Telethon Institute of Genetics and Medicine (TIGEM), Via P. Castellino 111, 80131 Naples, Italy.
Grzegorz Węgrzynthe Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
Diego L Medinathe High Content Screening Facility, Telethon Institute of Genetics and Medicine (TIGEM), Via P. Castellino 111, 80131 Naples, Italy, medina@tigem.it.
Andrea Ballabiothe High Content Screening Facility, Telethon Institute of Genetics and Medicine (TIGEM), Via P. Castellino 111, 80131 Naples, Italy, the Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, the Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas 77030, and Medical Genetics, Department of Pediatrics, Federico II University, Via Pansini 5, 80131 Naples, Italy.
Magdalena Gabig-CimińskaFrom the Laboratory of Molecular Biology (affiliated with the University of Gdańsk), Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Wita Stwosza 59, 80-308 Gdańsk, Poland, m.gabig@biol.ug.edu.pl.
Telethon Institute Of Genetics And Medicine · ITUniversity of Gdańsk · PLInstitute of Biochemistry and Biophysics, Polish Academy of Sciences · PLFederico II University Hospital · ITUniversity of Szczecin · PL

Funding

Telethon TGM11Z03
6 · The paper itself

Abstract

Genistein (5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) has been previously proposed as a potential drug for use in substrate reduction therapy for mucopolysaccharidoses, a group of inherited metabolic diseases caused by mutations leading to inefficient degradation of glycosaminoglycans (GAGs) in lysosomes. It was demonstrated that this isoflavone can cross the blood-brain barrier, making it an especially desirable potential drug for the treatment of neurological symptoms present in most lysosomal storage diseases. So far, no comprehensive genomic analyses have been performed to elucidate the molecular mechanisms underlying the effect elicited by genistein. Therefore, the aim of this work was to identify the genistein-modulated gene network regulating GAG biosynthesis and degradation, taking into consideration the entire lysosomal metabolism. Our analyses identified over 60 genes with known roles in lysosomal biogenesis and/or function whose expression was enhanced by genistein. Moreover, 19 genes whose products are involved in both GAG synthesis and degradation pathways were found to be remarkably differentially regulated by genistein treatment. We found a regulatory network linking genistein-mediated control of transcription factor EB (TFEB) gene expression, TFEB nuclear translocation, and activation of TFEB-dependent lysosome biogenesis to lysosomal metabolism. Our data indicate that the molecular mechanism of genistein action involves not only impairment of GAG synthesis but more importantly lysosomal enhancement via TFEB. These findings contribute to explaining the beneficial effects of genistein in lysosomal storage diseases as well as envisage new therapeutic approaches to treat these devastating diseases.

Indexed as

Gene Regulatory NetworksActive Transport, Cell NucleusBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCell LineGenisteinGlycosaminoglycansHumansLysosomesPhytoestrogensTranscription, GeneticBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsGenisteinGlycosaminoglycansPhytoestrogensTFEB protein, humanFlavonoidGene ExpressionGenisteinLysosomal MetabolismLysosomal Storage DiseaseMicroarrayNeurodegenerative DiseaseSubstrate Reduction TherapyTranscriptomic Network AnalysisTranscriptomics

Identifiers

PMID24770416
PMCPMC4059147
OpenAlexW2013629587

What OpenQuestion holds

Textmetadata
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.