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  1. Article ; Online: Special Issue "Role of NRF2 in Disease: Novel Molecular Mechanisms and Therapeutic Approaches II".

    Lastres-Becker, Isabel

    Biomolecules

    2023  Volume 13, Issue 5

    Abstract: This Special Issue (https://www [ ... ]. ...

    Abstract This Special Issue (https://www [...].
    MeSH term(s) NF-E2-Related Factor 2/genetics
    Chemical Substances NF-E2-Related Factor 2
    Language English
    Publishing date 2023-05-10
    Publishing country Switzerland
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom13050813
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Editorial: Tau Protein: Mechanisms From Health to Degeneration.

    Lastres-Becker, Isabel

    Frontiers in molecular neuroscience

    2021  Volume 14, Page(s) 743986

    Language English
    Publishing date 2021-11-01
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2021.743986
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Special Issue "Role of NRF2 in Disease: Novel Molecular Mechanisms and Therapeutic Approaches".

    Lastres-Becker, Isabel

    Biomolecules

    2021  Volume 11, Issue 2

    Abstract: This Special Issue on NRF2 (https://www [ ... ]. ...

    Abstract This Special Issue on NRF2 (https://www [...].
    MeSH term(s) Arsenic/toxicity ; Epigenesis, Genetic ; Humans ; Inflammation ; NF-E2-Related Factor 2/physiology ; Neoplasms/metabolism ; Neurodegenerative Diseases/metabolism ; Oxidation-Reduction ; Reactive Oxygen Species ; Sepsis/metabolism ; Skin Diseases/metabolism ; Up-Regulation
    Chemical Substances NF-E2-Related Factor 2 ; NFE2L2 protein, human ; Reactive Oxygen Species ; Arsenic (N712M78A8G)
    Language English
    Publishing date 2021-02-02
    Publishing country Switzerland
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom11020202
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Aging, NRF2, and TAU: A Perfect Match for Neurodegeneration?

    Brackhan, Mirjam / Arribas-Blazquez, Marina / Lastres-Becker, Isabel

    Antioxidants (Basel, Switzerland)

    2023  Volume 12, Issue 8

    Abstract: Although the trigger for the neurodegenerative disease process is unknown, the relevance of aging stands out as a major risk for the development of neurodegeneration. In this review, we highlighted the relationship between the different cellular ... ...

    Abstract Although the trigger for the neurodegenerative disease process is unknown, the relevance of aging stands out as a major risk for the development of neurodegeneration. In this review, we highlighted the relationship between the different cellular mechanisms that occur as a consequence of aging and transcription factor nuclear factor erythroid-2-related factor 2 (NRF2) and the connection with the TAU protein. We focused on the relevance of NRF2 in the main processes involved in neurodegeneration and associated with aging, such as genomic instability, protein degradation systems (proteasomes/autophagy), cellular senescence, and stem cell exhaustion, as well as inflammation. We also analyzed the effect of aging on TAU protein levels and its aggregation and spread process. Finally, we investigated the interconnection between NRF2 and TAU and the relevance of alterations in the NRF2 signaling pathway in both primary and secondary tauopathies. All these points highlight NRF2 as a possible therapeutic target for tauopathies.
    Language English
    Publishing date 2023-08-04
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox12081564
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Aging, NRF2, and TAU: A Perfect Match for Neurodegeneration?

    Brackhan, Mirjam / Arribas-Blazquez, Marina / Lastres-Becker, Isabel

    Antioxidants. 2023 Aug. 04, v. 12, no. 8

    2023  

    Abstract: Although the trigger for the neurodegenerative disease process is unknown, the relevance of aging stands out as a major risk for the development of neurodegeneration. In this review, we highlighted the relationship between the different cellular ... ...

    Abstract Although the trigger for the neurodegenerative disease process is unknown, the relevance of aging stands out as a major risk for the development of neurodegeneration. In this review, we highlighted the relationship between the different cellular mechanisms that occur as a consequence of aging and transcription factor nuclear factor erythroid-2-related factor 2 (NRF2) and the connection with the TAU protein. We focused on the relevance of NRF2 in the main processes involved in neurodegeneration and associated with aging, such as genomic instability, protein degradation systems (proteasomes/autophagy), cellular senescence, and stem cell exhaustion, as well as inflammation. We also analyzed the effect of aging on TAU protein levels and its aggregation and spread process. Finally, we investigated the interconnection between NRF2 and TAU and the relevance of alterations in the NRF2 signaling pathway in both primary and secondary tauopathies. All these points highlight NRF2 as a possible therapeutic target for tauopathies.
    Keywords autophagy ; cell senescence ; genetic instability ; inflammation ; neurodegenerative diseases ; protein degradation ; risk ; stem cells ; therapeutics ; transcription factors
    Language English
    Dates of publication 2023-0804
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article ; Online
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox12081564
    Database NAL-Catalogue (AGRICOLA)

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  6. Article: The Transcription Factor NRF2 Has Epigenetic Regulatory Functions Modulating HDACs, DNMTs, and miRNA Biogenesis.

    Silva-Llanes, Ignacio / Shin, Chang Hoon / Jiménez-Villegas, José / Gorospe, Myriam / Lastres-Becker, Isabel

    Antioxidants (Basel, Switzerland)

    2023  Volume 12, Issue 3

    Abstract: The epigenetic regulation of gene expression is a complex and tightly regulated process that defines cellular identity and is associated with health and disease processes. Oxidative stress is capable of inducing epigenetic modifications. The ... ...

    Abstract The epigenetic regulation of gene expression is a complex and tightly regulated process that defines cellular identity and is associated with health and disease processes. Oxidative stress is capable of inducing epigenetic modifications. The transcription factor NRF2 (nuclear factor erythroid-derived 2-like 2) is a master regulator of cellular homeostasis, regulating genes bearing antioxidant response elements (AREs) in their promoters. Here, we report the identification of ARE sequences in the promoter regions of genes encoding several epigenetic regulatory factors, such as histone deacetylases (HDACs), DNA methyltransferases (DNMTs), and proteins involved in microRNA biogenesis. In this research, we study this possibility by integrating bioinformatic, genetic, pharmacological, and molecular approaches. We found ARE sequences in the promoter regions of genes encoding several HDACs, DNMTs, and proteins involved in miRNA biogenesis. We confirmed that NRF2 regulates the production of these genes by studying NRF2-deficient cells and cells treated with dimethyl fumarate (DMF), an inducer of the NRF2 signaling pathway. In addition, we found that NRF2 could be involved in the target RNA-dependent microRNA degradation (TDMD) of miR-155-5p through its interaction with
    Language English
    Publishing date 2023-03-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox12030641
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The Transcription Factor NRF2 Has Epigenetic Regulatory Functions Modulating HDACs, DNMTs, and miRNA Biogenesis

    Silva-Llanes, Ignacio / Shin, Chang Hoon / Jiménez-Villegas, José / Gorospe, Myriam / Lastres-Becker, Isabel

    Antioxidants. 2023 Mar. 04, v. 12, no. 3

    2023  

    Abstract: The epigenetic regulation of gene expression is a complex and tightly regulated process that defines cellular identity and is associated with health and disease processes. Oxidative stress is capable of inducing epigenetic modifications. The ... ...

    Abstract The epigenetic regulation of gene expression is a complex and tightly regulated process that defines cellular identity and is associated with health and disease processes. Oxidative stress is capable of inducing epigenetic modifications. The transcription factor NRF2 (nuclear factor erythroid-derived 2-like 2) is a master regulator of cellular homeostasis, regulating genes bearing antioxidant response elements (AREs) in their promoters. Here, we report the identification of ARE sequences in the promoter regions of genes encoding several epigenetic regulatory factors, such as histone deacetylases (HDACs), DNA methyltransferases (DNMTs), and proteins involved in microRNA biogenesis. In this research, we study this possibility by integrating bioinformatic, genetic, pharmacological, and molecular approaches. We found ARE sequences in the promoter regions of genes encoding several HDACs, DNMTs, and proteins involved in miRNA biogenesis. We confirmed that NRF2 regulates the production of these genes by studying NRF2-deficient cells and cells treated with dimethyl fumarate (DMF), an inducer of the NRF2 signaling pathway. In addition, we found that NRF2 could be involved in the target RNA-dependent microRNA degradation (TDMD) of miR-155-5p through its interaction with Nfe2l2 mRNA. Our data indicate that NRF2 has an epigenetic regulatory function, complementing its traditional function and expanding the regulatory dimensions that should be considered when developing NRF2-centered therapeutic strategies.
    Keywords DNA methyltransferase ; antioxidant activity ; basic-leucine zipper transcription factors ; biogenesis ; bioinformatics ; dimethyl fumarate ; epigenetics ; gene expression regulation ; histone deacetylase ; homeostasis ; microRNA ; oxidative stress ; therapeutics
    Language English
    Dates of publication 2023-0304
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article ; Online
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox12030641
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: New Statement about NRF2 in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.

    Lastres-Becker, Isabel / de Lago, Eva / Martínez, Ana / Fernández-Ruiz, Javier

    Biomolecules

    2022  Volume 12, Issue 9

    Abstract: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are related neurodegenerative disorders displaying substantial overlay, although there are substantial differences at the molecular level. Currently, there is no effective treatment ... ...

    Abstract Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are related neurodegenerative disorders displaying substantial overlay, although there are substantial differences at the molecular level. Currently, there is no effective treatment for these diseases. The transcription factor NRF2 has been postulated as a promising therapeutic target as it is capable of modulating key pathogenic events affecting cellular homeostasis. However, there is little experimental evidence on the status of this pathway in both ALS and FTD. Therefore, in this work, we wanted to carry out an exhaustive analysis of this signaling pathway in both transgenic mouse models (ALS and FTD) and human samples from patients with sporadic ALS (sALS) versus controls. In samples from patients with sALS and in the transgenic model with overexpression of TDP-43
    MeSH term(s) Amyotrophic Lateral Sclerosis/metabolism ; Animals ; Antioxidants ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Frontotemporal Dementia/genetics ; Humans ; Mice ; Mice, Transgenic ; NF-E2-Related Factor 2/genetics
    Chemical Substances Antioxidants ; DNA-Binding Proteins ; NF-E2-Related Factor 2
    Language English
    Publishing date 2022-08-29
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom12091200
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: α-Synuclein Induces the GSK-3-Mediated Phosphorylation and Degradation of NURR1 and Loss of Dopaminergic Hallmarks.

    García-Yagüe, Ángel Juan / Lastres-Becker, Isabel / Stefanis, Leonidas / Vassilatis, Demetrios K / Cuadrado, Antonio

    Molecular neurobiology

    2021  Volume 58, Issue 12, Page(s) 6697–6711

    Abstract: In Parkinson's disease, the dysfunction of the dopaminergic nigrostriatal tract involves the loss of function of dopaminergic neurons of the substantia nigra pars compacta followed by death of these neurons. The functional recovery of these neurons ... ...

    Abstract In Parkinson's disease, the dysfunction of the dopaminergic nigrostriatal tract involves the loss of function of dopaminergic neurons of the substantia nigra pars compacta followed by death of these neurons. The functional recovery of these neurons requires a deep knowledge of the molecules that maintain the dopaminergic phenotype during adulthood and the mechanisms that subvert their activity. Previous studies have shown that transcription factor NURR1, involved in differentiation and maintenance of the dopaminergic phenotype, is downregulated by α-synuclein (α-SYN). In this study, we provide a mechanistic explanation to this finding by connecting α-SYN-induced activation of glycogen synthase kinase-3 (GSK-3) with NURR1 phosphorylation followed by proteasomal degradation. The use of sequential deletion mutants and single point mutants of NURR1 allowed the identification of a domain comprising amino acids 123-PSSPPTPSTPS-134 that is targeted by GSK-3 and leads to subsequent ubiquitination and proteasome degradation. This study provides a detailed analysis of the regulation of NURR1 stability by phosphorylation in synucleinopathies such as Parkinson's disease.
    MeSH term(s) Cell Line, Tumor ; Dopamine/metabolism ; Dopaminergic Neurons/drug effects ; Dopaminergic Neurons/metabolism ; Down-Regulation ; Gene Expression Regulation ; Glycogen Synthase Kinase 3/metabolism ; Humans ; Nuclear Receptor Subfamily 4, Group A, Member 2/metabolism ; Phosphorylation/drug effects ; alpha-Synuclein/pharmacology
    Chemical Substances NR4A2 protein, human ; Nuclear Receptor Subfamily 4, Group A, Member 2 ; alpha-Synuclein ; Glycogen Synthase Kinase 3 (EC 2.7.11.26) ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2021-10-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 645020-9
    ISSN 1559-1182 ; 0893-7648
    ISSN (online) 1559-1182
    ISSN 0893-7648
    DOI 10.1007/s12035-021-02558-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: NRF2 and Primary Cilia: An Emerging Partnership

    Martin-Hurtado, Ana / Lastres-Becker, Isabel / Cuadrado, Antonio / Garcia-Gonzalo, Francesc R

    Antioxidants. 2020 June 02, v. 9, no. 6

    2020  

    Abstract: When not dividing, many cell types target their centrosome to the plasma membrane, where it nucleates assembly of a primary cilium, an antenna-like signaling structure consisting of nine concentric microtubule pairs surrounded by membrane. Primary cilia ... ...

    Abstract When not dividing, many cell types target their centrosome to the plasma membrane, where it nucleates assembly of a primary cilium, an antenna-like signaling structure consisting of nine concentric microtubule pairs surrounded by membrane. Primary cilia play important pathophysiological roles in many tissues, their dysfunction being associated with cancer and ciliopathies, a diverse group of congenital human diseases. Several recent studies have unveiled functional connections between primary cilia and NRF2 (nuclear factor erythroid 2-related factor 2), the master transcription factor orchestrating cytoprotective responses to oxidative and other cellular stresses. These NRF2-cilia relationships are reciprocal: primary cilia, by promoting autophagy, downregulate NRF2 activity. In turn, NRF2 transcriptionally regulates genes involved in ciliogenesis and Hedgehog (Hh) signaling, a cilia-dependent pathway with major roles in embryogenesis, stem cell function and tumorigenesis. Nevertheless, while we found that NRF2 stimulates ciliogenesis and Hh signaling, a more recent study reported that NRF2 negatively affects these processes. Herein, we review the available evidence linking NRF2 to primary cilia, suggest possible explanations to reconcile seemingly contradictory data, and discuss what the emerging interplay between primary cilia and NRF2 may mean for human health and disease.
    Keywords autophagy ; carcinogenesis ; centrosomes ; cilia ; embryogenesis ; genes ; human diseases ; human health ; microtubules ; neoplasms ; plasma membrane ; stem cells ; transcription (genetics) ; transcription factors
    Language English
    Dates of publication 2020-0602
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox9060475
    Database NAL-Catalogue (AGRICOLA)

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