E2F4-Based Gene Therapy Mitigates the Phenotype of the Alzheimer’s Disease Mouse Model 5xFAD View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-11-11

AUTHORS

Noelia López-Sánchez, Alberto Garrido-García, Morgan Ramón-Landreau, Vanesa Cano-Daganzo, José M. Frade

ABSTRACT

After decades of unfruitful work, no effective therapies are available for Alzheimer’s disease (AD), likely due to its complex etiology that requires a multifactorial therapeutic approach. We have recently shown using transgenic mice that E2 factor 4 (E2F4), a transcription factor that regulates cell quiescence and tissue homeostasis, and controls gene networks affected in AD, represents a good candidate for a multifactorial targeting of AD. Here we show that the expression of a dominant negative form of human E2F4 (hE2F4DN), unable to become phosphorylated in a Thr-conserved motif known to modulate E2F4 activity, is an effective and safe AD multifactorial therapeutic agent. Neuronal expression of hE2F4DN in homozygous 5xFAD (h5xFAD) mice after systemic administration of an AAV.PHP.B-hSyn1.hE2F4DN vector reduced the production and accumulation of Aβ in the hippocampus, attenuated reactive astrocytosis and microgliosis, abolished neuronal tetraploidization, and prevented cognitive impairment evaluated by Y-maze and Morris water maze, without triggering side effects. This treatment also reversed other alterations observed in h5xFAD mice such as paw-clasping behavior and body weight loss. Our results indicate that E2F4DN-based gene therapy is a promising therapeutic approach against AD. More... »

PAGES

1-20

References to SciGraph publications

  • 2016-08-20. A common strategy for initiating the transition from proliferation to quiescence in CURRENT GENETICS
  • 2018-08-10. Gene therapy for neurological disorders: progress and prospects in NATURE REVIEWS DRUG DISCOVERY
  • 1982-06. Place navigation impaired in rats with hippocampal lesions in NATURE
  • 2019-07-03. E2F4 regulates transcriptional activation in mouse embryonic stem cells independently of the RB family in NATURE COMMUNICATIONS
  • 2007-02. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents in NATURE PROTOCOLS
  • 1999-12. Clinical features of Alzheimer’s disease in EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
  • 2016-02-01. Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain in NATURE BIOTECHNOLOGY
  • 2019-02-04. Regional protein expression in human Alzheimer’s brain correlates with disease severity in COMMUNICATIONS BIOLOGY
  • 2009-04-12. Enzymatic assembly of DNA molecules up to several hundred kilobases in NATURE METHODS
  • 2005-12-15. Woodchuck hepatitis virus post-transcriptional regulatory element deleted from X protein and promoter sequences enhances retroviral vector titer and expression in GENE THERAPY
  • 2016-04-21. Organization, evolution and functions of the human and mouse Ly6/uPAR family genes in HUMAN GENOMICS
  • <error retrieving object. in <ERROR RETRIEVING OBJECT
  • 2014-03-11. Optimization of AAV expression cassettes to improve packaging capacity and transgene expression in neurons in MOLECULAR BRAIN
  • 1970-12. Lack of a Long-term Effect of LSD on Y-maze Learning in Mice in NATURE
  • 2018-04-19. Construction of Transcriptional Regulatory Network of Alzheimer’s Disease Based on PANDA Algorithm in INTERDISCIPLINARY SCIENCES: COMPUTATIONAL LIFE SCIENCES
  • 2018-02-09. Prefoldin, a jellyfish-like molecular chaperone: functional cooperation with a group II chaperonin and beyond in BIOPHYSICAL REVIEWS
  • 2013-08-06. ERK-associated changes in E2F4 phosphorylation, localization and transcriptional activity during mitogenic stimulation in human intestinal epithelial crypt cells in BMC MOLECULAR AND CELL BIOLOGY
  • 2019. Amyloid-β and Tau at the Crossroads of Alzheimer’s Disease in TAU BIOLOGY
  • 1996-12-01. Phosphorylation State-Specific Antibodies in REGULATORY PROTEIN MODIFICATION
  • 2019-05-21. Epigenetic dysregulation of enhancers in neurons is associated with Alzheimer’s disease pathology and cognitive symptoms in NATURE COMMUNICATIONS
  • 2016-07-19. Cellular GFP Toxicity and Immunogenicity: Potential Confounders in in Vivo Cell Tracking Experiments in STEM CELL REVIEWS AND REPORTS
  • 2018-09-25. Cell cycle reentry triggers hyperploidization and synaptic dysfunction followed by delayed cell death in differentiated cortical neurons in SCIENTIFIC REPORTS
  • 1999-12. The Lewy body variant of Alzheimer’s disease: clinical, pathophysiological and conceptual issues in EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s13311-021-01151-1

    DOI

    http://dx.doi.org/10.1007/s13311-021-01151-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1142535396

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/34766258


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1109", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Neurosciences", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute, 28002, Madrid, Spain", 
              "id": "http://www.grid.ac/institutes/grid.419043.b", 
              "name": [
                "Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute, 28002, Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "L\u00f3pez-S\u00e1nchez", 
            "givenName": "Noelia", 
            "id": "sg:person.0704321117.10", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0704321117.10"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute, 28002, Madrid, Spain", 
              "id": "http://www.grid.ac/institutes/grid.419043.b", 
              "name": [
                "Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute, 28002, Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Garrido-Garc\u00eda", 
            "givenName": "Alberto", 
            "id": "sg:person.012504325501.58", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012504325501.58"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute, 28002, Madrid, Spain", 
              "id": "http://www.grid.ac/institutes/grid.419043.b", 
              "name": [
                "Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute, 28002, Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Ram\u00f3n-Landreau", 
            "givenName": "Morgan", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute, 28002, Madrid, Spain", 
              "id": "http://www.grid.ac/institutes/grid.419043.b", 
              "name": [
                "Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute, 28002, Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Cano-Daganzo", 
            "givenName": "Vanesa", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute, 28002, Madrid, Spain", 
              "id": "http://www.grid.ac/institutes/grid.419043.b", 
              "name": [
                "Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute, 28002, Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Frade", 
            "givenName": "Jos\u00e9 M.", 
            "id": "sg:person.01015521046.05", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01015521046.05"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1186/s40246-016-0074-2", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035042155", 
              "https://doi.org/10.1186/s40246-016-0074-2"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.gt.3302698", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048455565", 
              "https://doi.org/10.1038/sj.gt.3302698"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41467-019-10101-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1114941004", 
              "https://doi.org/10.1038/s41467-019-10101-7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41467-019-10901-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1117696822", 
              "https://doi.org/10.1038/s41467-019-10901-x"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/pl00014176", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012555731", 
              "https://doi.org/10.1007/pl00014176"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nmeth.1318", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040405189", 
              "https://doi.org/10.1038/nmeth.1318"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s42003-018-0254-9", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1111913060", 
              "https://doi.org/10.1038/s42003-018-0254-9"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1756-6606-7-17", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034812332", 
              "https://doi.org/10.1186/1756-6606-7-17"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1385/0-89603-415-1:219", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014052775", 
              "https://doi.org/10.1385/0-89603-415-1:219"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/978-981-32-9358-8_16", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1125103461", 
              "https://doi.org/10.1007/978-981-32-9358-8_16"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s12551-018-0400-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1100921257", 
              "https://doi.org/10.1007/s12551-018-0400-0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/2281107a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039895069", 
              "https://doi.org/10.1038/2281107a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s004060050101", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029408748", 
              "https://doi.org/10.1007/s004060050101"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41598-018-32708-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1107108089", 
              "https://doi.org/10.1038/s41598-018-32708-4"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00294-016-0640-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006676870", 
              "https://doi.org/10.1007/s00294-016-0640-0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s12539-018-0297-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1103453798", 
              "https://doi.org/10.1007/s12539-018-0297-0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s12015-016-9670-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030769050", 
              "https://doi.org/10.1007/s12015-016-9670-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/297681a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051409362", 
              "https://doi.org/10.1038/297681a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41434-018-0005-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1101401384", 
              "https://doi.org/10.1038/s41434-018-0005-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrd.2018.110", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1106079063", 
              "https://doi.org/10.1038/nrd.2018.110"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.3440", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018502206", 
              "https://doi.org/10.1038/nbt.3440"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1471-2121-14-33", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022727477", 
              "https://doi.org/10.1186/1471-2121-14-33"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nprot.2007.44", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012369107", 
              "https://doi.org/10.1038/nprot.2007.44"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2021-11-11", 
        "datePublishedReg": "2021-11-11", 
        "description": "After decades of unfruitful work, no effective therapies are available for Alzheimer\u2019s disease (AD), likely due to its complex etiology that requires a multifactorial therapeutic approach. We have recently shown using transgenic mice that E2 factor 4 (E2F4), a transcription factor that regulates cell quiescence and tissue homeostasis, and controls gene networks affected in AD, represents a good candidate for a multifactorial targeting of AD. Here we show that the expression of a dominant negative form of human E2F4 (hE2F4DN), unable to become phosphorylated in a Thr-conserved motif known to modulate E2F4 activity, is an effective and safe AD multifactorial therapeutic agent. Neuronal expression of hE2F4DN in homozygous 5xFAD (h5xFAD) mice after systemic administration of an AAV.PHP.B-hSyn1.hE2F4DN vector reduced the production and accumulation of A\u03b2 in the hippocampus, attenuated reactive astrocytosis and microgliosis, abolished neuronal tetraploidization, and prevented cognitive impairment evaluated by Y-maze and Morris water maze, without triggering side effects. This treatment also reversed other alterations observed in h5xFAD mice such as paw-clasping behavior and body weight loss. Our results indicate that E2F4DN-based gene therapy is a promising therapeutic approach against AD.", 
        "genre": "article", 
        "id": "sg:pub.10.1007/s13311-021-01151-1", 
        "inLanguage": "en", 
        "isAccessibleForFree": true, 
        "isPartOf": [
          {
            "id": "sg:journal.1294839", 
            "issn": [
              "1933-7213", 
              "1878-7479"
            ], 
            "name": "Neurotherapeutics", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }
        ], 
        "keywords": [
          "Alzheimer's disease", 
          "therapeutic approaches", 
          "body weight loss", 
          "accumulation of A\u03b2", 
          "multifactorial therapeutic approach", 
          "promising therapeutic approach", 
          "Morris water maze", 
          "gene therapy", 
          "reactive astrocytosis", 
          "effective therapy", 
          "systemic administration", 
          "neuronal expression", 
          "side effects", 
          "transgenic mice", 
          "water maze", 
          "cognitive impairment", 
          "therapeutic agents", 
          "complex etiology", 
          "therapy", 
          "weight loss", 
          "mice", 
          "factor 4", 
          "disease", 
          "cell quiescence", 
          "dominant negative form", 
          "maze", 
          "tissue homeostasis", 
          "microgliosis", 
          "astrocytosis", 
          "hippocampus", 
          "transcription factors", 
          "etiology", 
          "expression", 
          "administration", 
          "A\u03b2", 
          "impairment", 
          "treatment", 
          "AAV", 
          "negative form", 
          "homeostasis", 
          "alterations", 
          "phenotype", 
          "targeting", 
          "agents", 
          "factors", 
          "activity", 
          "quiescence", 
          "accumulation", 
          "good candidate", 
          "loss", 
          "effect", 
          "candidates", 
          "Thr", 
          "gene networks", 
          "decades", 
          "production", 
          "results", 
          "approach", 
          "form", 
          "tetraploidization", 
          "vector", 
          "behavior", 
          "motif", 
          "work", 
          "network", 
          "unfruitful work", 
          "E2 factor 4", 
          "multifactorial targeting", 
          "safe AD multifactorial therapeutic agent", 
          "AD multifactorial therapeutic agent", 
          "multifactorial therapeutic agent", 
          "hE2F4DN", 
          "homozygous 5xFAD (h5xFAD) mice", 
          "hSyn1", 
          "hE2F4DN vector", 
          "neuronal tetraploidization", 
          "h5xFAD mice", 
          "E2F4DN-based gene therapy", 
          "Alzheimer\u2019s Disease Mouse Model 5xFAD", 
          "\u2019s Disease Mouse Model 5xFAD", 
          "Mouse Model 5xFAD", 
          "Model 5xFAD"
        ], 
        "name": "E2F4-Based Gene Therapy Mitigates the Phenotype of the Alzheimer\u2019s Disease Mouse Model 5xFAD", 
        "pagination": "1-20", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1142535396"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1007/s13311-021-01151-1"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "34766258"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1007/s13311-021-01151-1", 
          "https://app.dimensions.ai/details/publication/pub.1142535396"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-01-01T19:01", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20220101/entities/gbq_results/article/article_878.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1007/s13311-021-01151-1"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s13311-021-01151-1'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s13311-021-01151-1'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s13311-021-01151-1'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s13311-021-01151-1'


     

    This table displays all metadata directly associated to this object as RDF triples.

    256 TRIPLES      22 PREDICATES      129 URIs      98 LITERALS      5 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1007/s13311-021-01151-1 schema:about anzsrc-for:11
    2 anzsrc-for:1109
    3 schema:author N7b9bd34cc6134d4895abb0fa0289a232
    4 schema:citation sg:pub.10.1007/978-981-32-9358-8_16
    5 sg:pub.10.1007/pl00014176
    6 sg:pub.10.1007/s00294-016-0640-0
    7 sg:pub.10.1007/s004060050101
    8 sg:pub.10.1007/s12015-016-9670-8
    9 sg:pub.10.1007/s12539-018-0297-0
    10 sg:pub.10.1007/s12551-018-0400-0
    11 sg:pub.10.1038/2281107a0
    12 sg:pub.10.1038/297681a0
    13 sg:pub.10.1038/nbt.3440
    14 sg:pub.10.1038/nmeth.1318
    15 sg:pub.10.1038/nprot.2007.44
    16 sg:pub.10.1038/nrd.2018.110
    17 sg:pub.10.1038/s41434-018-0005-z
    18 sg:pub.10.1038/s41467-019-10101-7
    19 sg:pub.10.1038/s41467-019-10901-x
    20 sg:pub.10.1038/s41598-018-32708-4
    21 sg:pub.10.1038/s42003-018-0254-9
    22 sg:pub.10.1038/sj.gt.3302698
    23 sg:pub.10.1186/1471-2121-14-33
    24 sg:pub.10.1186/1756-6606-7-17
    25 sg:pub.10.1186/s40246-016-0074-2
    26 sg:pub.10.1385/0-89603-415-1:219
    27 schema:datePublished 2021-11-11
    28 schema:datePublishedReg 2021-11-11
    29 schema:description After decades of unfruitful work, no effective therapies are available for Alzheimer’s disease (AD), likely due to its complex etiology that requires a multifactorial therapeutic approach. We have recently shown using transgenic mice that E2 factor 4 (E2F4), a transcription factor that regulates cell quiescence and tissue homeostasis, and controls gene networks affected in AD, represents a good candidate for a multifactorial targeting of AD. Here we show that the expression of a dominant negative form of human E2F4 (hE2F4DN), unable to become phosphorylated in a Thr-conserved motif known to modulate E2F4 activity, is an effective and safe AD multifactorial therapeutic agent. Neuronal expression of hE2F4DN in homozygous 5xFAD (h5xFAD) mice after systemic administration of an AAV.PHP.B-hSyn1.hE2F4DN vector reduced the production and accumulation of Aβ in the hippocampus, attenuated reactive astrocytosis and microgliosis, abolished neuronal tetraploidization, and prevented cognitive impairment evaluated by Y-maze and Morris water maze, without triggering side effects. This treatment also reversed other alterations observed in h5xFAD mice such as paw-clasping behavior and body weight loss. Our results indicate that E2F4DN-based gene therapy is a promising therapeutic approach against AD.
    30 schema:genre article
    31 schema:inLanguage en
    32 schema:isAccessibleForFree true
    33 schema:isPartOf sg:journal.1294839
    34 schema:keywords AAV
    35 AD multifactorial therapeutic agent
    36 Alzheimer's disease
    37 Alzheimer’s Disease Mouse Model 5xFAD
    38
    39 E2 factor 4
    40 E2F4DN-based gene therapy
    41 Model 5xFAD
    42 Morris water maze
    43 Mouse Model 5xFAD
    44 Thr
    45 accumulation
    46 accumulation of Aβ
    47 activity
    48 administration
    49 agents
    50 alterations
    51 approach
    52 astrocytosis
    53 behavior
    54 body weight loss
    55 candidates
    56 cell quiescence
    57 cognitive impairment
    58 complex etiology
    59 decades
    60 disease
    61 dominant negative form
    62 effect
    63 effective therapy
    64 etiology
    65 expression
    66 factor 4
    67 factors
    68 form
    69 gene networks
    70 gene therapy
    71 good candidate
    72 h5xFAD mice
    73 hE2F4DN
    74 hE2F4DN vector
    75 hSyn1
    76 hippocampus
    77 homeostasis
    78 homozygous 5xFAD (h5xFAD) mice
    79 impairment
    80 loss
    81 maze
    82 mice
    83 microgliosis
    84 motif
    85 multifactorial targeting
    86 multifactorial therapeutic agent
    87 multifactorial therapeutic approach
    88 negative form
    89 network
    90 neuronal expression
    91 neuronal tetraploidization
    92 phenotype
    93 production
    94 promising therapeutic approach
    95 quiescence
    96 reactive astrocytosis
    97 results
    98 safe AD multifactorial therapeutic agent
    99 side effects
    100 systemic administration
    101 targeting
    102 tetraploidization
    103 therapeutic agents
    104 therapeutic approaches
    105 therapy
    106 tissue homeostasis
    107 transcription factors
    108 transgenic mice
    109 treatment
    110 unfruitful work
    111 vector
    112 water maze
    113 weight loss
    114 work
    115 ’s Disease Mouse Model 5xFAD
    116 schema:name E2F4-Based Gene Therapy Mitigates the Phenotype of the Alzheimer’s Disease Mouse Model 5xFAD
    117 schema:pagination 1-20
    118 schema:productId N189f08e109574b64b5ec17a8af36328f
    119 N9b7b18e71e9442c1948a5e4844547faa
    120 Nc91d38ffdeab4656af0e24e9f2088e16
    121 schema:sameAs https://app.dimensions.ai/details/publication/pub.1142535396
    122 https://doi.org/10.1007/s13311-021-01151-1
    123 schema:sdDatePublished 2022-01-01T19:01
    124 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    125 schema:sdPublisher N84a7685537734e30812006a09e502570
    126 schema:url https://doi.org/10.1007/s13311-021-01151-1
    127 sgo:license sg:explorer/license/
    128 sgo:sdDataset articles
    129 rdf:type schema:ScholarlyArticle
    130 N189f08e109574b64b5ec17a8af36328f schema:name pubmed_id
    131 schema:value 34766258
    132 rdf:type schema:PropertyValue
    133 N39739d4d508341edbb65c98570c1e3ed rdf:first Na6841de0776e4fd6ae98e367554f087a
    134 rdf:rest Neaefb96b48bb4511964748a3e96b6954
    135 N521c1d2439864e83bf3a8f20d31f5283 rdf:first Nd2b0cfbcc22a47e9886b5fcc614114e1
    136 rdf:rest N39739d4d508341edbb65c98570c1e3ed
    137 N7b9bd34cc6134d4895abb0fa0289a232 rdf:first sg:person.0704321117.10
    138 rdf:rest Nf4dd59531946437284e521403407d093
    139 N84a7685537734e30812006a09e502570 schema:name Springer Nature - SN SciGraph project
    140 rdf:type schema:Organization
    141 N9b7b18e71e9442c1948a5e4844547faa schema:name dimensions_id
    142 schema:value pub.1142535396
    143 rdf:type schema:PropertyValue
    144 Na6841de0776e4fd6ae98e367554f087a schema:affiliation grid-institutes:grid.419043.b
    145 schema:familyName Cano-Daganzo
    146 schema:givenName Vanesa
    147 rdf:type schema:Person
    148 Nc91d38ffdeab4656af0e24e9f2088e16 schema:name doi
    149 schema:value 10.1007/s13311-021-01151-1
    150 rdf:type schema:PropertyValue
    151 Nd2b0cfbcc22a47e9886b5fcc614114e1 schema:affiliation grid-institutes:grid.419043.b
    152 schema:familyName Ramón-Landreau
    153 schema:givenName Morgan
    154 rdf:type schema:Person
    155 Neaefb96b48bb4511964748a3e96b6954 rdf:first sg:person.01015521046.05
    156 rdf:rest rdf:nil
    157 Nf4dd59531946437284e521403407d093 rdf:first sg:person.012504325501.58
    158 rdf:rest N521c1d2439864e83bf3a8f20d31f5283
    159 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    160 schema:name Medical and Health Sciences
    161 rdf:type schema:DefinedTerm
    162 anzsrc-for:1109 schema:inDefinedTermSet anzsrc-for:
    163 schema:name Neurosciences
    164 rdf:type schema:DefinedTerm
    165 sg:journal.1294839 schema:issn 1878-7479
    166 1933-7213
    167 schema:name Neurotherapeutics
    168 schema:publisher Springer Nature
    169 rdf:type schema:Periodical
    170 sg:person.01015521046.05 schema:affiliation grid-institutes:grid.419043.b
    171 schema:familyName Frade
    172 schema:givenName José M.
    173 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01015521046.05
    174 rdf:type schema:Person
    175 sg:person.012504325501.58 schema:affiliation grid-institutes:grid.419043.b
    176 schema:familyName Garrido-García
    177 schema:givenName Alberto
    178 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012504325501.58
    179 rdf:type schema:Person
    180 sg:person.0704321117.10 schema:affiliation grid-institutes:grid.419043.b
    181 schema:familyName López-Sánchez
    182 schema:givenName Noelia
    183 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0704321117.10
    184 rdf:type schema:Person
    185 sg:pub.10.1007/978-981-32-9358-8_16 schema:sameAs https://app.dimensions.ai/details/publication/pub.1125103461
    186 https://doi.org/10.1007/978-981-32-9358-8_16
    187 rdf:type schema:CreativeWork
    188 sg:pub.10.1007/pl00014176 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012555731
    189 https://doi.org/10.1007/pl00014176
    190 rdf:type schema:CreativeWork
    191 sg:pub.10.1007/s00294-016-0640-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006676870
    192 https://doi.org/10.1007/s00294-016-0640-0
    193 rdf:type schema:CreativeWork
    194 sg:pub.10.1007/s004060050101 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029408748
    195 https://doi.org/10.1007/s004060050101
    196 rdf:type schema:CreativeWork
    197 sg:pub.10.1007/s12015-016-9670-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030769050
    198 https://doi.org/10.1007/s12015-016-9670-8
    199 rdf:type schema:CreativeWork
    200 sg:pub.10.1007/s12539-018-0297-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1103453798
    201 https://doi.org/10.1007/s12539-018-0297-0
    202 rdf:type schema:CreativeWork
    203 sg:pub.10.1007/s12551-018-0400-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1100921257
    204 https://doi.org/10.1007/s12551-018-0400-0
    205 rdf:type schema:CreativeWork
    206 sg:pub.10.1038/2281107a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039895069
    207 https://doi.org/10.1038/2281107a0
    208 rdf:type schema:CreativeWork
    209 sg:pub.10.1038/297681a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051409362
    210 https://doi.org/10.1038/297681a0
    211 rdf:type schema:CreativeWork
    212 sg:pub.10.1038/nbt.3440 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018502206
    213 https://doi.org/10.1038/nbt.3440
    214 rdf:type schema:CreativeWork
    215 sg:pub.10.1038/nmeth.1318 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040405189
    216 https://doi.org/10.1038/nmeth.1318
    217 rdf:type schema:CreativeWork
    218 sg:pub.10.1038/nprot.2007.44 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012369107
    219 https://doi.org/10.1038/nprot.2007.44
    220 rdf:type schema:CreativeWork
    221 sg:pub.10.1038/nrd.2018.110 schema:sameAs https://app.dimensions.ai/details/publication/pub.1106079063
    222 https://doi.org/10.1038/nrd.2018.110
    223 rdf:type schema:CreativeWork
    224 sg:pub.10.1038/s41434-018-0005-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1101401384
    225 https://doi.org/10.1038/s41434-018-0005-z
    226 rdf:type schema:CreativeWork
    227 sg:pub.10.1038/s41467-019-10101-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1114941004
    228 https://doi.org/10.1038/s41467-019-10101-7
    229 rdf:type schema:CreativeWork
    230 sg:pub.10.1038/s41467-019-10901-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1117696822
    231 https://doi.org/10.1038/s41467-019-10901-x
    232 rdf:type schema:CreativeWork
    233 sg:pub.10.1038/s41598-018-32708-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1107108089
    234 https://doi.org/10.1038/s41598-018-32708-4
    235 rdf:type schema:CreativeWork
    236 sg:pub.10.1038/s42003-018-0254-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1111913060
    237 https://doi.org/10.1038/s42003-018-0254-9
    238 rdf:type schema:CreativeWork
    239 sg:pub.10.1038/sj.gt.3302698 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048455565
    240 https://doi.org/10.1038/sj.gt.3302698
    241 rdf:type schema:CreativeWork
    242 sg:pub.10.1186/1471-2121-14-33 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022727477
    243 https://doi.org/10.1186/1471-2121-14-33
    244 rdf:type schema:CreativeWork
    245 sg:pub.10.1186/1756-6606-7-17 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034812332
    246 https://doi.org/10.1186/1756-6606-7-17
    247 rdf:type schema:CreativeWork
    248 sg:pub.10.1186/s40246-016-0074-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035042155
    249 https://doi.org/10.1186/s40246-016-0074-2
    250 rdf:type schema:CreativeWork
    251 sg:pub.10.1385/0-89603-415-1:219 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014052775
    252 https://doi.org/10.1385/0-89603-415-1:219
    253 rdf:type schema:CreativeWork
    254 grid-institutes:grid.419043.b schema:alternateName Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute, 28002, Madrid, Spain
    255 schema:name Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute, 28002, Madrid, Spain
    256 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...