Type

Journal Article

Authors

Marina A Lynch
Mary Reilly
Peter McGuirk
William McCormack
Brian Keogh
Ana Rubio-Araiz
Edel Hennessy
Claire L McDonald

Subjects

Biochemistry

Topics
presenilin 1 neurodegenerative diseases therapeutic targets 1 protein receptor activation toll like receptor amyloid protein precursor microglial activation

Inhibiting TLR2 activation attenuates amyloid accumulation and glial activation in a mouse model of Alzheimer's disease. (2016)

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-β (Aβ) 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 Aβ 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 Aβ 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.
Collections Ireland -> Trinity College Dublin -> PubMed

Full list of authors on original publication

Marina A Lynch, Mary Reilly, Peter McGuirk, William McCormack, Brian Keogh, Ana Rubio-Araiz, Edel Hennessy, Claire L McDonald

Experts in our system

1
Marina Annetta Lynch
Trinity College Dublin
Total Publications: 80