Oxytocin Nanogels Inhibit Innate Inflammatory Response for Early Intervention in Alzheimer's Disease.
ACS Appl Mater Interfaces
; 14(19): 21822-21835, 2022 May 18.
Article
em En
| MEDLINE
| ID: mdl-35510352
ABSTRACT
Prevention of Alzheimer's disease (AD) is a global imperative, but reliable early interventions are currently lacking. Microglia-mediated chronic neuroinflammation is thought to occur in the early stage of AD and plays a critical role in AD pathogenesis. Here, oxytocin (OT)-loaded angiopep-2-modified chitosan nanogels (AOC NGs) were designed for early treatment of AD via inhibiting innate inflammatory response. Through the effective transcytosis of angiopep-2, AOC NGs were driven intravenously to cross the blood-brain barrier, enter the brain, and enrich in brain areas affected by AD. A large amount of OT was then released and specifically bound to the pathological upregulated OT receptor, thus effectively inhibiting microglial activation and reducing inflammatory cytokine levels through blocking the ERK/p38 MAPK and COX-2/iNOS NF-κB signaling pathways. Consecutive weekly intravenous administration of AOC NGs into 12-week-old young APP/PS1 mice, representing the early stage of AD, remarkably slowed the progression of Aß deposition and neuronal apoptosis in the APP/PS1 mice as they aged and ultimately prevented cognitive impairment and delayed hippocampal atrophy. Together, the findings suggest that AOC NGs, which show good biosafety, can serve as a promising therapeutic candidate to combat neuroinflammation for early prevention of AD.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
ACS Appl Mater Interfaces
Assunto da revista:
BIOTECNOLOGIA
/
ENGENHARIA BIOMEDICA
Ano de publicação:
2022
Tipo de documento:
Article