Targeting Alzheimer's disease with multimodal polypeptide-based nanoconjugates
Por:
A. DURO-CASTANO, C. BORRAS, V. HERRANZ-PEREZ, M. BLANCO-GANDIA, I. CONEJOS-SANCHEZ, A. ARMINAN, C. MAS-BARGUES, M. INGLES, J. MINARRO, M. RODRIGUEZ-ARIAS, J. GARCIA-VERDUGO, J. VINA and M. VICENT
Publicada:
1 mar 2021
Resumen:
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 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.
Filiaciones:
:
Ctr Invest Principe Felipe CIPF, Polymer Therapeut Lab, Av Eduardo Primo Yufera 3, Valencia 46012, Spain
UCL, Chem Dept, Mol Bion Lab, 20 Gordon St, London WC1H 0AJ, England
C. BORRAS:
Univ Valencia, Fac Med, CIBERFES ISCIII, Grp Invest FRESHAGE,Dept Fisiol,INCLIVA, Av Blasco Ibanez 15, Valencia 46010, Spain
V. HERRANZ-PEREZ:
Univ Valencia, Cavanilles Inst Biodivers & Evolutionary Biol, Lab Comparat Neurobiol, CIBERNED, Valencia 46980, Spain
Univ Jaume 1, Fac Hlth Sci, Predept Unit Med, Castellon de La Plana 12071, Spain
M. BLANCO-GANDIA:
Univ Zaragoza, Fac Ciencias Sociales & Humanas, Dept Psicol & Sociol, Teruel, Spain
:
Ctr Invest Principe Felipe CIPF, Polymer Therapeut Lab, Av Eduardo Primo Yufera 3, Valencia 46012, Spain
:
Ctr Invest Principe Felipe CIPF, Polymer Therapeut Lab, Av Eduardo Primo Yufera 3, Valencia 46012, Spain
C. MAS-BARGUES:
Univ Valencia, Fac Med, CIBERFES ISCIII, Grp Invest FRESHAGE,Dept Fisiol,INCLIVA, Av Blasco Ibanez 15, Valencia 46010, Spain
M. INGLES:
Univ Valencia, Fac Psicol, Dept Psicobiol, Unidad Invest Psicobiol Drogodependencias, Valencia, Spain
J. MINARRO:
Univ Valencia, Fac Psicol, Dept Psicobiol, Unidad Invest Psicobiol Drogodependencias, Valencia, Spain
M. RODRIGUEZ-ARIAS:
Univ Valencia, Fac Psicol, Dept Psicobiol, Unidad Invest Psicobiol Drogodependencias, Valencia, Spain
:
Univ Valencia, Cavanilles Inst Biodivers & Evolutionary Biol, Lab Comparat Neurobiol, CIBERNED, Valencia 46980, Spain
J. VINA:
Univ Valencia, Fac Med, CIBERFES ISCIII, Grp Invest FRESHAGE,Dept Fisiol,INCLIVA, Av Blasco Ibanez 15, Valencia 46010, Spain
:
Ctr Invest Principe Felipe CIPF, Polymer Therapeut Lab, Av Eduardo Primo Yufera 3, Valencia 46012, Spain
Gold, Green Published
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