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To elucidate the mechanisms leading from abnormal protein deposition to neuronal injury, we have performed a detailed network analysis of genes differentially expressed in several mouse prion models.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We found a master regulatory core of genes related to immune response controlling other genes involved in prion protein replication and accumulation, and neuronal cell death. This regulatory core determines the existence of two stable states that are consistent with the transcriptome analysis comparing prion infected versus uninfected mouse brain. An <jats:italic>in silico<\/jats:italic> perturbation analysis demonstrates that core genes are individually capable of triggering the transition and that the network remains locked once the diseased state is reached.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We hypothesize that this locking may be the cause of the sustained immune response observed in prion disease. Our analysis supports the hypothesis that sustained brain inflammation is the main pathogenic process leading to neuronal dysfunction and loss, which, in turn, leads to clinical symptoms in prion disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-6-132","type":"journal-article","created":{"date-parts":[[2012,10,15]],"date-time":"2012-10-15T17:30:44Z","timestamp":1350322244000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Gene regulatory network analysis supports inflammation as a key neurodegeneration process in prion disease"],"prefix":"10.1186","volume":"6","author":[{"given":"Isaac","family":"Crespo","sequence":"first","affiliation":[]},{"given":"Kirsten","family":"Roomp","sequence":"additional","affiliation":[]},{"given":"Wiktor","family":"Jurkowski","sequence":"additional","affiliation":[]},{"given":"Hiroaki","family":"Kitano","sequence":"additional","affiliation":[]},{"given":"Antonio","family":"del Sol","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2012,10,15]]},"reference":[{"key":"1060_CR1","doi-asserted-by":"publisher","first-page":"a006833","DOI":"10.1101\/cshperspect.a006833","volume":"3","author":"DW Colby","year":"2011","unstructured":"Colby DW, Prusiner SB: Prions. 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