Targeting Alzheimer’s disease with multimodal polypeptide-based nanoconjugates
| Autor: | Aroa Duro-Castano, Inmaculada Conejos-Sánchez, Ana Armiñán, M. C. Blanco-Gandía, Marta Rodríguez-Arias, Juan R. Viña, V. Herranz-Pérez, Marta Inglés, Cristina Mas-Bargues, María J. Vicent, José Miñarro, José Manuel García-Verdugo, Consuelo Borrás |
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| Rok vydání: | 2021 |
| Předmět: |
Alzheimer’s disease (AD)
Mice Transgenic Nanoconjugates Hippocampal formation Hippocampus Neuroprotection AD treatment Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Alzheimer Disease Bisdemethoxycurcumin Animals Olfactory memory Research Articles 030304 developmental biology 0303 health sciences Amyloid beta-Peptides Multidisciplinary Polyglutamate biology SciAdv r-articles Life Sciences 3. Good health Olfactory bulb Disease Models Animal Applied Sciences and Engineering chemistry biology.protein Neuroscience 030217 neurology & neurosurgery Research Article Neurotrophin |
| Zdroj: | Science Advances r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) instname r-CIPF: Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) Centro de Investigación Principe Felipe (CIPF) Zaguán: Repositorio Digital de la Universidad de Zaragoza Universidad de Zaragoza Zaguán. Repositorio Digital de la Universidad de Zaragoza r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA Repositori Universitat Jaume I Universitat Jaume I |
| ISSN: | 2375-2548 |
| Popis: | LRP1-targeted St-Cl–polyglutamate conjugates as multivalent neuroprotective/neurotrophic therapeutics for Alzheimer’s disease. 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 β 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. |
| Databáze: | OpenAIRE |
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