{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T12:00:49Z","timestamp":1720094449834},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,3,15]],"date-time":"2007-03-15T00:00:00Z","timestamp":1173916800000},"content-version":"vor","delay-in-days":73,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2007,1]]},"abstract":"<jats:p><jats:bold><jats:sc>Abstract<\/jats:sc>:\u2002<\/jats:bold>  <jats:bold>The conversion of the prion protein (PrP) into a protease\u2010resistant isoform (PrP<jats:sup>Res<\/jats:sup>) is considered the pathogenic event responsible for prion encephalopathies. Microglia activation accompanies PrP<jats:sup>Res<\/jats:sup> deposition representing an early event in the progression of these diseases. It is now believed that microglial cells play a worsening, if not causative, role in prion\u2010induced neuronal death, through the release of proinflammatory and neurotoxic molecules. Indeed, <jats:italic>in vitro<\/jats:italic> observations have demonstrated that PrP<jats:sup>Res<\/jats:sup> and the synthetic prion fragment PrP106\u2010126 induce neuronal death by activating microglial to migrate in the lesion area and secrete cytokines. Recently, we and others have demonstrated that the recombinant peptide, corresponding to the protease\u2010resistant portion of PrP encompassing the amino acids 90\u2010231 (PrP90\u2010231), when \u03b2\u2010structured, is toxic for neuronal cells, <jats:italic>in vitro<\/jats:italic>. Here we report that PrP90\u2010231 induces activation of N9 microglial cells, characterized by cell proliferation arrest and increased secretion of different cytokines (RANTES, GCSF, and IL\u201012)<\/jats:bold>\n          <jats:bold>. Moreover, the treatment of N9 cells with PrP90\u2010231 elicited inducible nitric oxide synthase (i\u2010NOS) expression, nitric oxide release, and a delayed (15 min to 1 h of treatment) extracellular signal\u2010regulated kinases 1\/2 (ERK1\/2) phosphorylation\/activation. Although ERK1\/2 is known to regulate proliferative and differentiative events, we show that its blockade, using the specific MEK inhibitor PD98059, did not prevent PrP90\u2010231\u2010induced inhibition of N9 cell proliferation. To our knowledge, this is the first evidence that a recombinant PrP<jats:sup>Res<\/jats:sup>\u2010like peptide elicits microglial activation <jats:italic>in vitro,<\/jats:italic> thus representing a potentially important tool to develop possible therapeutic strategies to target prion\u2010induced brain inflammation.<\/jats:bold> <\/jats:p>","DOI":"10.1196\/annals.1397.092","type":"journal-article","created":{"date-parts":[[2007,4,3]],"date-time":"2007-04-03T19:27:49Z","timestamp":1175628469000},"page":"258-270","source":"Crossref","is-referenced-by-count":14,"title":["Amino\u2010Terminally Truncated Prion Protein PrP90\u2010231 Induces Microglial Activation <i>in 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