Amyloid-ß peptide-specific DARPins as a novel class of potential therapeutics for Alzheimer disease.
J Biol Chem
; 289(39): 27080-27089, 2014 Sep 26.
Article
em En
| MEDLINE
| ID: mdl-25118284
ABSTRACT
Passive immunization with anti-amyloid-ß peptide (Aß) antibodies is effective in animal models of Alzheimer disease. With the advent of efficient in vitro selection technologies, the novel class of designed ankyrin repeat proteins (DARPins) presents an attractive alternative to the immunoglobulin scaffold. DARPins are small and highly stable proteins with a compact modular architecture ideal for high affinity protein-protein interactions. In this report, we describe the selection, binding profile, and epitope analysis of Aß-specific DARPins. We further showed their ability to delay Aß aggregation and prevent Aß-mediated neurotoxicity in vitro. To demonstrate their therapeutic potential in vivo, mono- and trivalent Aß-specific DARPins (D23 and 3×D23) were infused intracerebroventricularly into the brains of 11-month-old Tg2576 mice over 4 weeks. Both D23 and 3×D23 treatments were shown to result in improved cognitive performance and reduced soluble Aß levels. These findings demonstrate the therapeutic potential of Aß-specific DARPins for the treatment of Alzheimer disease.
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Base de dados:
MEDLINE
Assunto principal:
Precursor de Proteína beta-Amiloide
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Repetição de Anquirina
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Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article