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• W2167547115 endingPage "5503" @default.
• W2167547115 startingPage "5493" @default.
• W2167547115 abstract "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 &lt; 0.05). Glial PAR2 activation increased expression of formyl peptide receptor-2 (p &lt; 0.01), a cognate receptor for a fibrillar 42-aa form of β-amyloid (Aβ1–42), enhanced microglia-mediated proinflammatory responses, and suppressed astrocytic IL-4 expression, resulting in neuronal death (p &lt; 0.05). Conversely, neuronal PAR2 activation protected human neurons against the toxic effects of Aβ1–42 (p &lt; 0.05), a key component of AD neuropathogenesis. Amyloid precursor protein-transgenic mice, displayed glial fibrillary acidic protein and IL-4 induction (p &lt; 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 Aβ1–42 implantation, exhibited enhanced IL-4 induction and less neuroinflammation (p &lt; 0.05), together with improved neurobehavioral outcomes (p &lt; 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 Aβ1–42-mediated neurodegeneration." @default.
• W2167547115 created "2016-06-24" @default.
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• W2167547115 date "2007-10-15" @default.
• W2167547115 modified "2023-10-17" @default.
• W2167547115 title "Proteinase-Activated Receptor-2 Exerts Protective and Pathogenic Cell Type-Specific Effects in Alzheimer’s Disease" @default.
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• W2167547115 doi "https://doi.org/10.4049/jimmunol.179.8.5493" @default.
• W2167547115 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17911636" @default.
• W2167547115 hasPublicationYear "2007" @default.
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