هجدهمین کنگره فیزیولو‍ژی و فارماکولوژی ایران , 2007-08-26

Title : ( Proteinase activated receptor-2 exerts protective and pathogenic cell-type specific effects in Alzheimer s disease )

Authors: Christopher Power , Avril J. Keller , Amir Afkhami Goli , Farshid Noorbakhsh , Nathalie Vergnolle , David Westaway , Jack H. Jhamandas , Patricia Andrade-Gordon , Morley D. Hollenberg , Hosseinali Arab , Richard H. Dyck ,

Citation: BibTeX | EndNote

Abstract

The proteinase-activated receptors (PARs) are a novel family of G protein-coupled receptors, and their effects in neurodegenerative diseases remain uncertain. Alzheimer s disease (AD) is a neurodegenerative disorder defined by misfolded protein accumulation with concurrent neuroinflammation and neuronal death. We report suppression of proteinase-activated receptor-2 (PAR2) expression in neurons of brains from AD patients, whereas PAR2 expression was increased in proximate glial cells, together with up-regulation of proinflammatory cytokines and chemokines and reduced IL-4 expression (p < 0.05). Glial PAR2 activation increased expression of formyl peptide receptor-2 (p < 0.01), a cognate receptor for a fibrillar 42-aa form of beta-amyloid (Abeta(1-42)), enhanced microglia-mediated proinflammatory responses, and suppressed astrocytic IL-4 expression, resulting in neuronal death (p < 0.05). Conversely, neuronal PAR2 activation protected human neurons against the toxic effects of Abeta(1-42) (p < 0.05), a key component of AD neuropathogenesis. Amyloid precursor protein-transgenic mice, displayed glial fibrillary acidic protein and IL-4 induction (p < 0.05) in the absence of proinflammatory gene up-regulation and neuronal injury, whereas PAR2 was up-regulated at this early stage of disease progression. PAR2-deficient mice, after hippocampal Abeta(1-42) implantation, exhibited enhanced IL-4 induction and less neuroinflammation (p < 0.05), together with improved neurobehavioral outcomes (p < 0.05). Thus, PAR2 exerted protective properties in neurons, but its activation in glia was pathogenic with secretion of neurotoxic factors and suppression of astrocytic anti-inflammatory mechanisms contributing to Abeta(1-42)-mediated neurodegeneration.

Keywords

, proteinase-activated receptors, neuroinflammation, Abeta(1-42), Alzheimer s disease
برای دانلود از شناسه و رمز عبور پرتال پویا استفاده کنید.

@inproceedings{paperid:1017838,
author = {Christopher Power and Avril J. Keller and Afkhami Goli, Amir and Farshid Noorbakhsh and Nathalie Vergnolle and David Westaway and Jack H. Jhamandas and Patricia Andrade-Gordon and Morley D. Hollenberg and Hosseinali Arab and Richard H. Dyck},
title = {Proteinase activated receptor-2 exerts protective and pathogenic cell-type specific effects in Alzheimer s disease},
booktitle = {هجدهمین کنگره فیزیولو‍ژی و فارماکولوژی ایران},
year = {2007},
location = {مشهد, IRAN},
keywords = {proteinase-activated receptors; neuroinflammation; Abeta(1-42); Alzheimer s disease},
}

[Download]

%0 Conference Proceedings
%T Proteinase activated receptor-2 exerts protective and pathogenic cell-type specific effects in Alzheimer s disease
%A Christopher Power
%A Avril J. Keller
%A Afkhami Goli, Amir
%A Farshid Noorbakhsh
%A Nathalie Vergnolle
%A David Westaway
%A Jack H. Jhamandas
%A Patricia Andrade-Gordon
%A Morley D. Hollenberg
%A Hosseinali Arab
%A Richard H. Dyck
%J هجدهمین کنگره فیزیولو‍ژی و فارماکولوژی ایران
%D 2007

[Download]