Erythrocyte membrane-encapsulated celecoxib improves the cognitive decline of Alzheimer's disease by concurrently inducing neurogenesis and reducing apoptosis in APP/PS1 transgenic mice.
Biomaterials
; 145: 106-127, 2017 Nov.
Article
em En
| MEDLINE
| ID: mdl-28865290
ABSTRACT
Alzheimer's disease (AD) is characterized by the loss of neurogenesis and excessive induction of apoptosis. The induction of neurogenesis and inhibition of apoptosis may be a promising therapeutic approach to combating the disease. Celecoxib (CB), a cyclooxygenase-2 specific inhibitor, could offer neuroprotection. Specifically, the CB-encapsulated erythrocyte membranes (CB-RBCMs) sustained the release of CB over a period of 72 h in vitro and exhibited high brain biodistribution efficiency following intranasal administration, which resulted in the clearance of aggregated ß-amyloid proteins (Aß) in neurons. The high accumulation of the CB-RBCMs in neurons resulted in a decrease in the neurotoxicity of CB and an increase in the migratory activity of neurons, and alleviated cognitive decline in APP/PS1 transgenic (Tg) mice. Indeed, COX-2 metabolic products including prostaglandin E2 (PGE2) and PGD2, PGE2 induced neurogenesis by enhancing the expression of SOD2 and 14-3-3ζ, and PGD2 stimulated apoptosis by increasing the expression of BIK and decreasing the expression of ARRB1. To this end, the CB-RBCMs achieved better effects on concurrently increasing neurogenesis and decreasing apoptosis than the phospholipid membrane-encapsulated CB liposomes (CB-PSPD-LPs), which are critical for the development and progression of AD. Therefore, CB-RBCMs provide a rational design to treat AD by promoting the self-repairing capacity of the brain.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
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Apoptose
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Membrana Eritrocítica
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Presenilina-1
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Neurogênese
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Doença de Alzheimer
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Disfunção Cognitiva
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Celecoxib
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Biomaterials
Ano de publicação:
2017
Tipo de documento:
Article