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Alliance"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:p>\n                    Selective neuronal vulnerability is common in neurodegenerative diseases but poorly understood. In genetic prion diseases, including fatal familial insomnia (FFI) and Creutzfeldt\u2013Jakob disease (CJD), different mutations in the\n                    <jats:italic>Prnp<\/jats:italic>\n                    gene manifest as clinically and neuropathologically distinct diseases. Here we report with electroencephalography studies that theta waves are mildly increased in 21 mo old knock-in mice modeling FFI and CJD and that sleep is mildy affected in FFI mice. To define affected cell types, we analyzed cell type\u2013specific translatomes from six neuron types of 9 mo old FFI and CJD mice. Somatostatin (SST) neurons responded the strongest in both diseases, with unexpectedly high overlap in genes and pathways. Functional analyses revealed up-regulation of neurodegenerative disease pathways and ribosome and mitochondria biogenesis, and down-regulation of synaptic function and small GTPase-mediated signaling in FFI, implicating down-regulation of mTOR signaling as the root of these changes. In contrast, responses in glutamatergic cerebellar neurons were disease-specific. The high similarity in SST neurons of FFI and CJD mice suggests that a common therapy may be beneficial for multiple genetic prion diseases.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202201530","type":"journal-article","created":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T10:20:14Z","timestamp":1664792414000},"page":"e202201530","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Translatome profiling in fatal familial insomnia implicates TOR signaling in somatostatin neurons"],"prefix":"10.26508","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4731-5002","authenticated-orcid":true,"given":"Susanne","family":"Bauer","sequence":"first","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, Wallenberg Center for Molecular Medicine, Link\u00f6ping University, Link\u00f6ping, 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