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  1. Article ; Online: Monitoring Nrf2/ARE Pathway Activity with a New Zebrafish Reporter System.

    Badenetti, Lorenzo / Manzoli, Rosa / Rubin, Michela / Cozza, Giorgio / Moro, Enrico

    International journal of molecular sciences

    2023  Volume 24, Issue 7

    Abstract: Among multiple cytoprotective mechanisms, eukaryotic cells exhibit a complex transcriptional program relying on the Nrf2 transcription factor, which is generally recruited upon biological stressors including oxidative-stress-based cellular insults. The ... ...

    Abstract Among multiple cytoprotective mechanisms, eukaryotic cells exhibit a complex transcriptional program relying on the Nrf2 transcription factor, which is generally recruited upon biological stressors including oxidative-stress-based cellular insults. The relevance of this master regulator has remarkably emerged in recent years in several research fields such as cancer, inflammatory disorders and age-related neurological diseases. Here, we document the generation and characterization of a novel Nrf2/ARE pathway biosensor fish which exhibits a dynamic spatiotemporal expression profile during the early developmental stages. The transgenic line is responsive to known Nrf2 pathway modulators but also to Edaravone, which direct activity on the Nrf2 pathway has never been documented in a live transgenic fish model. We also show that the reporter is faithfully activated during fin regeneration, and its degree of expression is slightly affected in a glucocerebrosidase (Gba1) morphant zebrafish model. Therefore, this novel transgenic fish may represent a valuable tool to be exploited for the characterization of zebrafish models of human diseases, as well as for primary high-throughput drug screening.
    MeSH term(s) Animals ; Humans ; Zebrafish/genetics ; Zebrafish/metabolism ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Oxidative Stress/genetics ; Animals, Genetically Modified/genetics ; Antioxidants/metabolism ; Zebrafish Proteins/metabolism
    Chemical Substances NF-E2-Related Factor 2 ; Antioxidants ; Zebrafish Proteins
    Language English
    Publishing date 2023-04-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24076804
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Lysosomal Function and Axon Guidance: Is There a Meaningful Liaison?

    Manzoli, Rosa / Badenetti, Lorenzo / Rubin, Michela / Moro, Enrico

    Biomolecules

    2021  Volume 11, Issue 2

    Abstract: Axonal trajectories and neural circuit activities strongly rely on a complex system of molecular cues that finely orchestrate the patterning of neural commissures. Several of these axon guidance molecules undergo continuous recycling during brain ... ...

    Abstract Axonal trajectories and neural circuit activities strongly rely on a complex system of molecular cues that finely orchestrate the patterning of neural commissures. Several of these axon guidance molecules undergo continuous recycling during brain development, according to incompletely understood intracellular mechanisms, that in part rely on endocytic and autophagic cascades. Based on their pivotal role in both pathways, lysosomes are emerging as a key hub in the sophisticated regulation of axonal guidance cue delivery, localization, and function. In this review, we will attempt to collect some of the most relevant research on the tight connection between lysosomal function and axon guidance regulation, providing some proof of concepts that may be helpful to understanding the relation between lysosomal storage disorders and neurodegenerative diseases.
    MeSH term(s) Autophagy ; Axon Guidance ; Axons/metabolism ; Brain/metabolism ; Endosomes/metabolism ; Ephrins/metabolism ; Humans ; Lysosomal Storage Diseases/metabolism ; Lysosomes/chemistry ; Lysosomes/metabolism ; Netrins/metabolism ; Neurodegenerative Diseases/metabolism ; Neurons/metabolism ; Semaphorins/metabolism
    Chemical Substances Ephrins ; Netrins ; Semaphorins
    Language English
    Publishing date 2021-01-29
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom11020191
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Mucopolysaccharidosis type II zebrafish model exhibits early impaired proteasomal-mediated degradation of the axon guidance receptor Dcc.

    Manzoli, Rosa / Badenetti, Lorenzo / Bruzzone, Matteo / Macario, Maria Carla / Rubin, Michela / Dal Maschio, Marco / Roveri, Antonella / Moro, Enrico

    Cell death & disease

    2024  Volume 15, Issue 4, Page(s) 269

    Abstract: Most of the patients affected by neuronopathic forms of Mucopolysaccharidosis type II (MPS II), a rare lysosomal storage disorder caused by defects in iduronate-2-sulfatase (IDS) activity, exhibit early neurological defects associated with white matter ... ...

    Abstract Most of the patients affected by neuronopathic forms of Mucopolysaccharidosis type II (MPS II), a rare lysosomal storage disorder caused by defects in iduronate-2-sulfatase (IDS) activity, exhibit early neurological defects associated with white matter lesions and progressive behavioural abnormalities. While neuronal degeneration has been largely described in experimental models and human patients, more subtle neuronal pathogenic defects remain still underexplored. In this work, we discovered that the axon guidance receptor Deleted in Colorectal Cancer (Dcc) is significantly dysregulated in the brain of ids mutant zebrafish since embryonic stages. In addition, thanks to the establishment of neuronal-enriched primary cell cultures, we identified defective proteasomal degradation as one of the main pathways underlying Dcc upregulation in ids mutant conditions. Furthermore, ids mutant fish-derived primary neurons displayed higher levels of polyubiquitinated proteins and P62, suggesting a wider defect in protein degradation. Finally, we show that ids mutant larvae display an atypical response to anxiety-inducing stimuli, hence mimicking one of the characteristic features of MPS II patients. Our study provides an additional relevant frame to MPS II pathogenesis, supporting the concept that multiple developmental defects concur with early childhood behavioural abnormalities.
    MeSH term(s) Animals ; Axon Guidance ; Brain/metabolism ; Iduronate Sulfatase/metabolism ; Mucopolysaccharidosis II/metabolism ; Nervous System Diseases/pathology ; Zebrafish/metabolism
    Chemical Substances Iduronate Sulfatase (EC 3.1.6.13) ; dcc protein, zebrafish
    Language English
    Publishing date 2024-04-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/s41419-024-06661-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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