Journal article Open Access

Targeting Alzheimer's disease with multimodal polypeptide-based nanoconjugates

Duro-Castano, A; Borras, C; Herranz-Pérez, V; Blanco-Gandía, MC; Conejos-Sánchez, I; Armiñán, A; Mas-Bargues, C; Inglés, M; Miñarro, J; Rodríguez-Arias, M; García-Verdugo, JM; Viña, J; Vicent, MJ


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    "description": "<p>Alzheimer&#39;s disease (AD), the most prevalent form of dementia, remains incurable mainly due to our failings in the search for effective pharmacological strategies. Here, we describe the development of targeted multimodal polypeptide-based nanoconjugates as potential AD treatments. Treatment with polypeptide nanoconjugates bearing propargylamine moieties and bisdemethoxycurcumin or genistein afforded neuroprotection and displayed neurotrophic effects, as evidenced by an increase in dendritic density of pyramidal neurons in organotypic hippocampal culture. The additional conjugation of the Angiopep-2 targeting moiety enhanced nanoconjugate passage through the blood-brain barrier and modulated brain distribution with nanoconjugate accumulation in neurogenic areas, including the olfactory bulb. Nanoconjugate treatment effectively reduced neurotoxic &beta; amyloid aggregate levels and rescued impairments to olfactory memory and object recognition in APP/PS1 transgenic AD model mice. Overall, this study provides a description of a targeted multimodal polyglutamate-based nanoconjugate with neuroprotective and neurotrophic potential for AD treatment.</p>", 
    "license": {
      "id": "CC-BY-4.0"
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    "title": "Targeting Alzheimer's disease with multimodal polypeptide-based nanoconjugates", 
    "journal": {
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      "issue": "13", 
      "pages": "eabf9180", 
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    "publication_date": "2021-03-29", 
    "creators": [
      {
        "affiliation": "Polymer Therapeutics Lab., Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF), Av. Eduardo Primo Y\u00fafera 3, 46012 Valencia, Spain.", 
        "name": "Duro-Castano, A"
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        "affiliation": "Grupo de Investigaci\u00f3n FRESHAGE, Departamento de Fisiolog\u00eda, Facultad de Medicina, Univ.. Valencia, CIBERFES-ISCIII, INCLIVA, Av. Blasco Ib\u00e1\u00f1ez 15, 46010 Valencia, Spain.", 
        "name": "Borras, C"
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        "affiliation": "Laboratory of Comparative Neurobiology, Cavanilles Institute of Biodiversity and Evolutionary Biology, Univ. Val\u00e8ncia, CIBERNED, 46980 Valencia, Spain AND Predepartamental Unit of Medicine, Faculty of Health Sciences, Univ. Jaume I, 12071 Castell\u00f3 de la Plana, Spain.", 
        "name": "Herranz-P\u00e9rez, V"
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      {
        "affiliation": "Departamento de Psicolog\u00eda y Sociolog\u00eda, Facultad de Ciencias Sociales y Humanas, Univ. Zaragoza, Teruel, Spain.", 
        "name": "Blanco-Gand\u00eda, MC"
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        "affiliation": "Polymer Therapeutics Lab., Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF), Av. Eduardo Primo Y\u00fafera 3, 46012 Valencia, Spain.", 
        "name": "Conejos-S\u00e1nchez, I"
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      {
        "affiliation": "Polymer Therapeutics Lab., Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF), Av. Eduardo Primo Y\u00fafera 3, 46012 Valencia, Spain.", 
        "name": "Armi\u00f1\u00e1n, A"
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        "name": "Mas-Bargues, C"
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      {
        "affiliation": "Unidad de Investigaci\u00f3n Psicobiolog\u00eda de las Drogodependencias, Departamento de Psicobiolog\u00eda, Facultad de Psicolog\u00eda, Univ. Valencia, Valencia, Spain.", 
        "name": "Ingl\u00e9s, M"
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        "affiliation": "Unidad de Investigaci\u00f3n Psicobiolog\u00eda de las Drogodependencias, Departamento de Psicobiolog\u00eda, Facultad de Psicolog\u00eda, Univ. Valencia, Valencia, Spain.", 
        "name": "Mi\u00f1arro, J"
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        "affiliation": "Unidad de Investigaci\u00f3n Psicobiolog\u00eda de las Drogodependencias, Departamento de Psicobiolog\u00eda, Facultad de Psicolog\u00eda, Univ. Valencia, Valencia, Spain.", 
        "name": "Rodr\u00edguez-Arias, M"
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        "affiliation": "Laboratory of Comparative Neurobiology, Cavanilles Institute of Biodiversity and Evolutionary Biology, Univ. Val\u00e8ncia, CIBERNED, 46980 Valencia, Spain.", 
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