Inhibiting TLR2 activation attenuates amyloid accumulation and glial activation in a mouse model of Alzheimer's disease.
Brain Behav Immun
; 58: 191-200, 2016 Nov.
Article
em En
| MEDLINE
| ID: mdl-27422717
ABSTRACT
The effects of Toll-like receptor (TLR) activation in peripheral cells are well characterized but, although several TLRs are expressed on cells of the brain, the consequences of their activation on neuronal function remain to be fully investigated, particularly in the context of assessing their potential as therapeutic targets in neurodegenerative diseases. Several endogenous TLR ligands have been identified, many of which are soluble factors released from cells exposed to stressors. In addition, amyloid-ß (Aß) the main constituent of the amyloid plaques in Alzheimer's disease (AD), activates TLR2, although it has also been shown to bind to several other receptors. The objective of this study was to determine whether activation of TLR2 played a role in the developing inflammatory changes and Aß accumulation in a mouse model of AD. Wild type and transgenic mice that overexpress amyloid precursor protein and presenilin 1 (APP/PS1 mice) were treated with anti-TLR2 antibody for 7months from the age of 7-14months. We demonstrate that microglial and astroglial activation, as assessed by MHCII, CD68 and GFAP immunoreactivity was decreased in anti-TLR2 antibody-treated compared with control (IgG)-treated mice. This was associated with reduced Aß plaque burden and improved performance in spatial learning. The data suggest that continued TLR2 activation contributes to the developing neuroinflammation and pathology and may be provide a strategy for limiting the progression of AD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Astrócitos
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Microglia
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Placa Amiloide
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Receptor 2 Toll-Like
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Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Brain Behav Immun
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
CEREBRO
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PSICOFISIOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Irlanda