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Activated microglia play a pivotal role in the progression of AD by either clearing amyloid \u03b2 peptide (A\u03b2) deposits through uptake of A\u03b2 or releasing cytotoxic substances and proinflammatory cytokines. Here, we investigated the effect of norepinephrine on A\u03b2 uptake and clearance by murine microglia and explored the underlying mechanisms. We found that murine microglia cell line N9 and primary microglia expressed \u03b2<jats:sub>2<\/jats:sub>adrenergic receptor (AR) but not \u03b2<jats:sub>1<\/jats:sub>and \u03b2<jats:sub>3<\/jats:sub>AR. Norepinephrine and isoproterenol upregulated the expression of A\u03b2 receptor mFPR2, a mouse homolog of human formyl peptide receptor FPR2, through activation of \u03b2<jats:sub>2<\/jats:sub>AR in microglia. Norepinephrine also induced mFPR2 expression in mouse brain. Activation of \u03b2<jats:sub>2<\/jats:sub>AR in microglia promoted A\u03b2<jats:sub>42<\/jats:sub>uptake through upregulation of mFPR2 and enhanced spontaneous cell migration but had no effect on cell migration in response to mFPR2 agonists. Furthermore, activation of \u03b2<jats:sub>2<\/jats:sub>AR on microglia induced the expression of insulin-degrading enzyme and increased the degradation of A\u03b2<jats:sub>42<\/jats:sub>. Mechanistic studies showed that isoproterenol induced mFPR2 expression through ERK1\/2-NF-\u03baB and p38-NF-\u03baB signaling pathways. These findings suggest that noradrenergic innervation from LC is needed to maintain adequate A\u03b2 uptake and clearance by microglia, and norepinephrine is a link between neuron and microglia to orchestrate the host response to A\u03b2 in AD.<\/jats:p>","DOI":"10.1523\/jneurosci.2985-10.2010","type":"journal-article","created":{"date-parts":[[2010,9,1]],"date-time":"2010-09-01T18:34:04Z","timestamp":1283366044000},"page":"11848-11857","source":"Crossref","is-referenced-by-count":119,"title":["Norepinephrine Promotes Microglia to Uptake and Degrade Amyloid \u03b2 Peptide through Upregulation of Mouse Formyl Peptide Receptor 2 and Induction of Insulin-Degrading 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