102180 20241024130536.0 doi 10.1126/sciadv.abf9180 sideral 124138 ART-2021-124138 eng Duro-Castano, A. Targeting Alzheimer’s disease with multimodal polypeptide-based nanoconjugates 2021 Access copy available to the general public Unrestricted Alzheimer’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 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. Copyright info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 14.98 2021 MULTIDISCIPLINARY SCIENCES 7 / 74 = 0.095 2021 Q1 T1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Borrás, C. Herranz-Pérez, V. Blanco-Gandía, M.C. Universidad de Zaragoza (orcid)0000-0001-5990-1266 Conejos-Sánchez, I. Armiñán, A. Mas-Bargues, C. Inglés, M. Miñarro, J. Rodríguez-Arias, M. García-Verdugo, J.M. Viña, J. Vicent, M.J. 4009 735 Universidad de Zaragoza Dpto. Psicología y Sociología Área Psicolog.Evolut.Educac 7, 13 (2021), [16 pp] Sci. adv. Science advances 2375-2548 4440900 http://zaguan.unizar.es/record/102180/files/texto_completo.pdf Versión publicada 3736427 http://zaguan.unizar.es/record/102180/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:102180 articulos driver 2024-10-24-13:01:43 ARTICLE