Amelioration of amyloid-ß-induced deficits by DcR3 in an Alzheimer's disease model.
Mol Neurodegener
; 12(1): 30, 2017 04 24.
Article
em En
| MEDLINE
| ID: mdl-28438208
ABSTRACT
BACKGROUND:
Microglia mediate amyloid-beta peptide (Aß)-induced neuroinflammation, which is one of the key events in the pathogenesis of Alzheimer's disease (AD). Decoy receptor 3 (DcR3)/TNFRSF6B is a pleiotropic immunomodulator that promotes macrophage differentiation toward the M2 anti-inflammatory phenotype. Based on its role as an immunosupressor, we examined whether DcR3 could alleviate neuroinflammation and AD-like deficits in the central nervous system.METHOD:
We crossed human APP transgenic mice (line J20) with human DcR3 transgenic mice to generate wild-type, APP, DcR3, and APP/DcR3 mice for pathological analysis. The Morris water maze, fear conditioning test, open-field, and elevated-plus maze were used to access their cognitive behavioral changes. Furthermore, the pathological and immune profiles were examined by immunostaining, ELISA, Q-PCR, and IP. In vitro assays were designed to examine DcR3-mediated innate cytokine profile alteration and the potential protective mechanism.RESULTS:
We reported that DcR3 ameliorates hippocampus-dependent memory deficits and reduces amyloid plaque deposition in APP transgenic mouse. The protective mechanism of DcR3 mediates through interacting with heparan sulfate proteoglycans and activating IL-4+YM1+ M2a-like microglia that reduces Aß-induced proinflammatory cytokines and promotes phagocytosis ability of microglia.CONCLUSION:
The neuroprotective effect of DcR3 is mediated via modulating microglia activation into anti-inflammatory M2a phenotype, and upregulating DcR3 expression in the brain may be a potential therapeutic approach for AD.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Peptídeos beta-Amiloides
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Microglia
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Membro 6b de Receptores do Fator de Necrose Tumoral
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Doença de Alzheimer
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Transtornos da Memória
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Neurodegener
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Taiwan