165352 20230915090618.0 10.26508/lsa.202201530 doi pmid:36192034 pmid pmc:PMC9531780 pmc altmetric:136765970 altmetric DZNE-2022-01629 English 570 Bauer, Susanne 0000-0003-4731-5002 0 Translatome profiling in fatal familial insomnia implicates TOR signaling in somatostatin neurons. Heidelberg 2022 EMBO Press article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1668700233_26687 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Selective neuronal vulnerability is common in neurodegenerative diseases but poorly understood. In genetic prion diseases, including fatal familial insomnia (FFI) and Creutzfeldt-Jakob disease (CJD), different mutations in the Prnp 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-specific 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. 352 - Disease Mechanisms (POF4-352) G:(DE-HGF)POF4-352 POF4-352 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de Somatostatin 51110-01-1 NLM Chemicals TOR Serine-Threonine Kinases EC 2.7.11.1 NLM Chemicals Monomeric GTP-Binding Proteins EC 3.6.5.2 NLM Chemicals Animals MeSH Creutzfeldt-Jakob Syndrome: genetics MeSH Insomnia, Fatal Familial: genetics MeSH Mice MeSH Monomeric GTP-Binding Proteins: metabolism MeSH Neurodegenerative Diseases MeSH Neurons: metabolism MeSH Prion Diseases: genetics MeSH Somatostatin: genetics MeSH Somatostatin: metabolism MeSH TOR Serine-Threonine Kinases: genetics MeSH TOR Serine-Threonine Kinases: metabolism MeSH Dittrich, Lars P:(DE-2719)2811120 1 dzne Kaczmarczyk, Lech P:(DE-2719)2810486 2 dzne Schleif, Melvin P:(DE-2719)2810344 3 dzne Benfeitas, Rui 4 Jackson, Walker Scot P:(DE-2719)2810253 5 Last author dzne 10.26508/lsa.202201530 Vol. 5, no. 11, p. e202201530 - PERI:(DE-600)2948687-7 11 e202201530 Life science alliance 5 2022 2575-1077 OpenAccess http://pub.dzne.de/record/165352/files/DZNE-2022-01629.pdf OpenAccess pdfa http://pub.dzne.de/record/165352/files/DZNE-2022-01629.pdf?subformat=pdfa oai:pub.dzne.de:165352 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 1 P:(DE-2719)2811120 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 2 P:(DE-2719)2810486 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 3 P:(DE-2719)2810344 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 5 P:(DE-2719)2810253 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-352 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Disease Mechanisms 0 2022 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2020-09-11 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2020-09-11 Creative Commons Attribution CC BY 4.0 LIC:(DE-HGF)CCBY4 HGFVOC WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2020-09-11 Fees StatID:(DE-HGF)0700 StatID 2020-09-11 OpenAccess StatID:(DE-HGF)0510 StatID Article Processing Charges StatID:(DE-HGF)0561 StatID 2020-09-11 JCR StatID:(DE-HGF)0100 StatID LIFE SCI ALLIANCE : 2021 2023-03-31 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2023-03-31 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2023-03-31 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2022-02-08T19:01:09Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2022-02-08T19:01:09Z Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Blind peer review 2022-02-08T19:01:09Z DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2023-03-31 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2023-03-31 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2023-03-31 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2023-03-31 IF >= 5 StatID:(DE-HGF)9905 StatID LIFE SCI ALLIANCE : 2021 2023-03-31 I:(DE-2719)1013019 AG Jackson Selective Vulnerability of Neurodegenerative Diseases 0 journal VDB UNRESTRICTED I:(DE-2719)1013019 FullTexts