Home > Publications Database > Distribution of dipeptide repeat proteins in cellular models and C9orf72 mutation cases suggests link to transcriptional silencing. > print

001     138124
005     20240614120614.0
024 7 _ |a 10.1007/s00401-015-1450-z
|2 doi
024 7 _ |a pmid:26085200
|2 pmid
024 7 _ |a pmc:PMC4575390
|2 pmc
024 7 _ |a 0001-6322
|2 ISSN
024 7 _ |a 1432-0533
|2 ISSN
024 7 _ |a altmetric:4188262
|2 altmetric
037 _ _ |a DZNE-2020-04446
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Schludi, Martin H
|0 P:(DE-2719)2810746
|b 0
|e First author
|u dzne
245 _ _ |a Distribution of dipeptide repeat proteins in cellular models and C9orf72 mutation cases suggests link to transcriptional silencing.
260 _ _ |a Heidelberg
|c 2015
|b Springer
264 _ 1 |3 online
|2 Crossref
|b Springer Science and Business Media LLC
|c 2015-06-18
264 _ 1 |3 print
|2 Crossref
|b Springer Science and Business Media LLC
|c 2015-10-01
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1718288026_11706
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a A massive expansion of a GGGGCC repeat upstream of the C9orf72 coding region is the most common known cause of amyotrophic lateral sclerosis and frontotemporal dementia. Despite its intronic localization and lack of a canonical start codon, both strands are translated into aggregating dipeptide repeat (DPR) proteins: poly-GA, poly-GP, poly-GR, poly-PR and poly-PA. To address conflicting findings on the predominant toxicity of the different DPR species in model systems, we compared the expression pattern of the DPR proteins in rat primary neurons and postmortem brain and spinal cord of C9orf72 mutation patients. Only poly-GA overexpression closely mimicked the p62-positive neuronal cytoplasmic inclusions commonly observed for all DPR proteins in patients. In contrast, overexpressed poly-GR and poly-PR formed nucleolar p62-negative inclusions. In patients, most of the less common neuronal intranuclear DPR inclusions were para-nucleolar and p62 positive. Neuronal nucleoli in C9orf72 cases showed normal size and morphology regardless of the presence of poly-GR and poly-PR inclusions arguing against widespread nucleolar stress, reported in cellular models. Colocalization of para-nucleolar DPR inclusions with heterochromatin and a marker of transcriptional repression (H3K9me2) indicates a link to gene transcription. In contrast, we detected numerous intranuclear DPR inclusions not associated with nucleolar structures in ependymal and subependymal cells. In patients, neuronal inclusions of poly-GR, poly-GP and the poly-GA interacting protein Unc119 were less abundant than poly-GA inclusions, but showed similar regional and subcellular distribution. Regardless of neurodegeneration, all inclusions were most abundant in neocortex, hippocampus and thalamus, with few inclusions in brain stem and spinal cord. In the granular cell layer of the cerebellum, poly-GA and Unc119 inclusions were significantly more abundant in cases with FTLD than in cases with MND and FTLD/MND. Poly-PR inclusions were rare throughout the brain but significantly more abundant in the CA3/4 region of FTLD cases than in MND cases. Thus, although DPR distribution is not correlated with neurodegeneration spatially, it correlates with neuropathological subtypes.
536 _ _ |a 342 - Disease Mechanisms and Model Systems (POF3-342)
|0 G:(DE-HGF)POF3-342
|c POF3-342
|f POF III
|x 0
536 _ _ |a 344 - Clinical and Health Care Research (POF3-344)
|0 G:(DE-HGF)POF3-344
|c POF3-344
|f POF III
|x 1
542 _ _ |i 2015-06-18
|2 Crossref
|u http://creativecommons.org/licenses/by/4.0
588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a Adaptor Proteins, Signal Transducing
|2 NLM Chemicals
650 _ 7 |a C9orf72 Protein
|2 NLM Chemicals
650 _ 7 |a C9orf72 protein, human
|2 NLM Chemicals
650 _ 7 |a Proteins
|2 NLM Chemicals
650 _ 7 |a UNC119 protein, human
|2 NLM Chemicals
650 _ 2 |a Adaptor Proteins, Signal Transducing: metabolism
|2 MeSH
650 _ 2 |a Adult
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Brain: metabolism
|2 MeSH
650 _ 2 |a Brain: pathology
|2 MeSH
650 _ 2 |a C9orf72 Protein
|2 MeSH
650 _ 2 |a Cell Nucleolus: metabolism
|2 MeSH
650 _ 2 |a Cell Nucleolus: pathology
|2 MeSH
650 _ 2 |a Cohort Studies
|2 MeSH
650 _ 2 |a DNA Repeat Expansion
|2 MeSH
650 _ 2 |a Frontotemporal Lobar Degeneration: complications
|2 MeSH
650 _ 2 |a Frontotemporal Lobar Degeneration: genetics
|2 MeSH
650 _ 2 |a Frontotemporal Lobar Degeneration: metabolism
|2 MeSH
650 _ 2 |a Frontotemporal Lobar Degeneration: pathology
|2 MeSH
650 _ 2 |a Gene Silencing
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Inclusion Bodies: metabolism
|2 MeSH
650 _ 2 |a Inclusion Bodies: pathology
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Motor Neuron Disease: complications
|2 MeSH
650 _ 2 |a Motor Neuron Disease: genetics
|2 MeSH
650 _ 2 |a Motor Neuron Disease: metabolism
|2 MeSH
650 _ 2 |a Motor Neuron Disease: pathology
|2 MeSH
650 _ 2 |a Neuroglia: metabolism
|2 MeSH
650 _ 2 |a Neuroglia: pathology
|2 MeSH
650 _ 2 |a Neurons: metabolism
|2 MeSH
650 _ 2 |a Neurons: pathology
|2 MeSH
650 _ 2 |a Proteins: genetics
|2 MeSH
650 _ 2 |a Proteins: metabolism
|2 MeSH
650 _ 2 |a Rats
|2 MeSH
650 _ 2 |a Spinal Cord: metabolism
|2 MeSH
650 _ 2 |a Spinal Cord: pathology
|2 MeSH
700 1 _ |a May, Stephanie
|0 P:(DE-2719)2762699
|b 1
|u dzne
700 1 _ |a Grässer, Friedrich A
|b 2
700 1 _ |a Rentzsch, Kristin
|0 P:(DE-2719)2501892
|b 3
|u dzne
700 1 _ |a Kremmer, Elisabeth
|0 P:(DE-2719)9000167
|b 4
|u dzne
700 1 _ |a Küpper, Clemens
|0 P:(DE-2719)9000175
|b 5
|u dzne
700 1 _ |a Klopstock, Thomas
|0 P:(DE-2719)2810704
|b 6
|u dzne
700 1 _ |a Degeneration, German Consortium for Frontotemporal Lobar
|b 7
700 1 _ |a Alliance, Bavarian Brain Banking
|b 8
700 1 _ |a Arzberger, Thomas
|0 P:(DE-2719)2811333
|b 9
|e Corresponding author
|u dzne
700 1 _ |a Edbauer, Dieter
|0 P:(DE-2719)2231621
|b 10
|e Last author
|u dzne
700 1 _ |a Danek, Adrian
|0 P:(DE-HGF)0
|b 11
700 1 _ |a Diehl-Schmid, Janine
|0 P:(DE-HGF)0
|b 12
700 1 _ |a Fassbender, Klaus
|b 13
700 1 _ |a Förstl, Hans
|b 14
700 1 _ |a Kornhuber, Johannes
|b 15
700 1 _ |a Otto, Markus
|b 16
700 1 _ |a Ceballos-Baumann, Andres
|b 17
700 1 _ |a Dieterich, Marianne
|0 P:(DE-HGF)0
|b 18
700 1 _ |a Feuerecker, Regina
|b 19
700 1 _ |a Giese, Armin
|0 P:(DE-HGF)0
|b 20
700 1 _ |a Klünemann, Hans
|b 21
700 1 _ |a Kurz, Alexander
|b 22
700 1 _ |a Levin, Johannes
|0 P:(DE-HGF)0
|b 23
700 1 _ |a Lorenzl, Stefan
|b 24
700 1 _ |a Meyer, Thomas
|b 25
700 1 _ |a Nübling, Georg
|b 26
700 1 _ |a Roeber, Sigrun
|b 27
773 1 8 |a 10.1007/s00401-015-1450-z
|b : Springer Science and Business Media LLC, 2015-06-18
|n 4
|p 537-555
|3 journal-article
|2 Crossref
|t Acta Neuropathologica
|v 130
|y 2015
|x 0001-6322
773 _ _ |a 10.1007/s00401-015-1450-z
|g Vol. 130, no. 4, p. 537 - 555
|0 PERI:(DE-600)1458410-4
|n 4
|q 130:4<537 - 555
|p 537-555
|t Acta neuropathologica
|v 130
|y 2015
|x 0001-6322
856 4 _ |y OpenAccess
|u https://pub.dzne.de/record/138124/files/DZNE-2020-04446.pdf
856 4 _ |y OpenAccess
|x pdfa
|u https://pub.dzne.de/record/138124/files/DZNE-2020-04446.pdf?subformat=pdfa
856 7 _ |2 Pubmed Central
|u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575390
909 C O |o oai:pub.dzne.de:138124
|p openaire
|p open_access
|p VDB
|p driver
|p dnbdelivery
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 0
|6 P:(DE-2719)2810746
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 1
|6 P:(DE-2719)2762699
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 3
|6 P:(DE-2719)2501892
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 4
|6 P:(DE-2719)9000167
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 5
|6 P:(DE-2719)9000175
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 6
|6 P:(DE-2719)2810704
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 9
|6 P:(DE-2719)2811333
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 10
|6 P:(DE-2719)2231621
913 1 _ |a DE-HGF
|b Gesundheit
|l Erkrankungen des Nervensystems
|1 G:(DE-HGF)POF3-340
|0 G:(DE-HGF)POF3-342
|3 G:(DE-HGF)POF3
|2 G:(DE-HGF)POF3-300
|4 G:(DE-HGF)POF
|v Disease Mechanisms and Model Systems
|x 0
913 1 _ |a DE-HGF
|b Gesundheit
|l Erkrankungen des Nervensystems
|1 G:(DE-HGF)POF3-340
|0 G:(DE-HGF)POF3-344
|3 G:(DE-HGF)POF3
|2 G:(DE-HGF)POF3-300
|4 G:(DE-HGF)POF
|v Clinical and Health Care Research
|x 1
914 1 _ |y 2015
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1030
|2 StatID
|b Current Contents - Life Sciences
915 _ _ |a Creative Commons Attribution CC BY 4.0
|0 LIC:(DE-HGF)CCBY4
|2 HGFVOC
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0600
|2 StatID
|b Ebsco Academic Search
915 _ _ |a IF >= 15
|0 StatID:(DE-HGF)9915
|2 StatID
|b ACTA NEUROPATHOL : 2017
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b ACTA NEUROPATHOL : 2017
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
915 _ _ |a WoS
|0 StatID:(DE-HGF)0110
|2 StatID
|b Science Citation Index
915 _ _ |a WoS
|0 StatID:(DE-HGF)0111
|2 StatID
|b Science Citation Index Expanded
915 _ _ |a OpenAccess
|0 StatID:(DE-HGF)0510
|2 StatID
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b ASC
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0310
|2 StatID
|b NCBI Molecular Biology Database
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
915 _ _ |a Nationallizenz
|0 StatID:(DE-HGF)0420
|2 StatID
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
920 1 _ |0 I:(DE-2719)1110004
|k AG Edbauer
|l Cell Biology of Neurodegeneration
|x 0
920 1 _ |0 I:(DE-2719)5000050
|k Ext HZM
|l Ext HZM
|x 1
920 1 _ |0 I:(DE-2719)5000049
|k Ext LMU Klinik
|l Ext LMU Klinik
|x 2
920 1 _ |0 I:(DE-2719)1111016
|k AG Levin
|l Clinical Neurodegeneration
|x 3
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a UNRESTRICTED
980 _ _ |a I:(DE-2719)1110004
980 _ _ |a I:(DE-2719)5000050
980 _ _ |a I:(DE-2719)5000049
980 _ _ |a I:(DE-2719)1111016
980 1 _ |a FullTexts
999 C 5 |y 2013
|2 Crossref
|o PE Ash 2013
999 C 5 |y 2014
|2 Crossref
|o A Baborie 2014
999 C 5 |9 -- missing cx lookup --
|a 10.1093/jnen/63.4.329
|2 Crossref
|o 10.1093/jnen/63.4.329
999 C 5 |9 -- missing cx lookup --
|a 10.1007/s00401-013-1199-1
|2 Crossref
|o 10.1007/s00401-013-1199-1
999 C 5 |y 2015
|2 Crossref
|o J Chew 2015
999 C 5 |9 -- missing cx lookup --
|a 10.1634/stemcells.2005-0076
|2 Crossref
|o 10.1634/stemcells.2005-0076
999 C 5 |y 2013
|2 Crossref
|o S Ciura 2013
999 C 5 |y 2015
|2 Crossref
|o J Cooper-Knock 2015
999 C 5 |9 -- missing cx lookup --
|a 10.1093/brain/awu120
|2 Crossref
|o 10.1093/brain/awu120
999 C 5 |9 -- missing cx lookup --
|a 10.1186/2051-5960-2-70
|2 Crossref
|o 10.1186/2051-5960-2-70
999 C 5 |9 -- missing cx lookup --
|a 10.1016/j.neuron.2011.09.011
|2 Crossref
|o 10.1016/j.neuron.2011.09.011
999 C 5 |9 -- missing cx lookup --
|a 10.1038/mt.2010.206
|2 Crossref
|o 10.1038/mt.2010.206
999 C 5 |9 -- missing cx lookup --
|a 10.1136/jnnp-2013-306995
|2 Crossref
|o 10.1136/jnnp-2013-306995
999 C 5 |9 -- missing cx lookup --
|a 10.1186/alzrt145
|2 Crossref
|o 10.1186/alzrt145
999 C 5 |9 -- missing cx lookup --
|a 10.1523/JNEUROSCI.3372-12.2013
|2 Crossref
|o 10.1523/JNEUROSCI.3372-12.2013
999 C 5 |9 -- missing cx lookup --
|a 10.1007/s00401-013-1237-z
|2 Crossref
|o 10.1007/s00401-013-1237-z
999 C 5 |9 -- missing cx lookup --
|a 10.1007/s00401-013-1192-8
|2 Crossref
|o 10.1007/s00401-013-1192-8
999 C 5 |9 -- missing cx lookup --
|a 10.1016/S1474-4422(11)70261-7
|2 Crossref
|o 10.1016/S1474-4422(11)70261-7
999 C 5 |9 -- missing cx lookup --
|a 10.1016/j.virol.2009.11.023
|2 Crossref
|o 10.1016/j.virol.2009.11.023
999 C 5 |9 -- missing cx lookup --
|a 10.1038/nature13124
|2 Crossref
|o 10.1038/nature13124
999 C 5 |9 -- missing cx lookup --
|a 10.1016/j.tins.2012.01.002
|2 Crossref
|o 10.1016/j.tins.2012.01.002
999 C 5 |9 -- missing cx lookup --
|a 10.1002/ana.22615
|2 Crossref
|o 10.1002/ana.22615
999 C 5 |9 -- missing cx lookup --
|a 10.1126/science.1254917
|2 Crossref
|o 10.1126/science.1254917
999 C 5 |9 -- missing cx lookup --
|a 10.1091/mbc.E02-03-0122
|2 Crossref
|o 10.1091/mbc.E02-03-0122
999 C 5 |9 -- missing cx lookup --
|a 10.1073/pnas.1318835110
|2 Crossref
|o 10.1073/pnas.1318835110
999 C 5 |9 -- missing cx lookup --
|a 10.1038/onc.2010.469
|2 Crossref
|o 10.1038/onc.2010.469
999 C 5 |9 -- missing cx lookup --
|a 10.1016/j.celrep.2013.10.049
|2 Crossref
|o 10.1016/j.celrep.2013.10.049
999 C 5 |9 -- missing cx lookup --
|a 10.1007/s00401-014-1286-y
|2 Crossref
|o 10.1007/s00401-014-1286-y
999 C 5 |9 -- missing cx lookup --
|a 10.1007/s00401-013-1181-y
|2 Crossref
|o 10.1007/s00401-013-1181-y
999 C 5 |9 -- missing cx lookup --
|a 10.1093/brain/awr361
|2 Crossref
|o 10.1093/brain/awr361
999 C 5 |9 -- missing cx lookup --
|a 10.1186/alzrt144
|2 Crossref
|o 10.1186/alzrt144
999 C 5 |9 -- missing cx lookup --
|a 10.1002/ana.24296
|2 Crossref
|o 10.1002/ana.24296
999 C 5 |9 -- missing cx lookup --
|a 10.1016/j.neurobiolaging.2014.10.011
|2 Crossref
|o 10.1016/j.neurobiolaging.2014.10.011
999 C 5 |9 -- missing cx lookup --
|a 10.1007/s00401-014-1329-4
|2 Crossref
|o 10.1007/s00401-014-1329-4
999 C 5 |9 -- missing cx lookup --
|a 10.1126/science.1256800
|2 Crossref
|o 10.1126/science.1256800
999 C 5 |9 -- missing cx lookup --
|a 10.1007/s00401-013-1189-3
|2 Crossref
|o 10.1007/s00401-013-1189-3
999 C 5 |y 2013
|2 Crossref
|o K Mori 2013
999 C 5 |9 -- missing cx lookup --
|a 10.1016/j.jneumeth.2005.08.001
|2 Crossref
|o 10.1016/j.jneumeth.2005.08.001
999 C 5 |9 -- missing cx lookup --
|a 10.1111/j.1440-1789.2011.01267.x
|2 Crossref
|o 10.1111/j.1440-1789.2011.01267.x
999 C 5 |9 -- missing cx lookup --
|a 10.1101/cshperspect.a000679
|2 Crossref
|o 10.1101/cshperspect.a000679
999 C 5 |9 -- missing cx lookup --
|a 10.1007/s00401-014-1245-7
|2 Crossref
|o 10.1007/s00401-014-1245-7
999 C 5 |9 -- missing cx lookup --
|a 10.1016/j.neuron.2011.09.010
|2 Crossref
|o 10.1016/j.neuron.2011.09.010
999 C 5 |9 -- missing cx lookup --
|a 10.1007/s00401-014-1365-0
|2 Crossref
|o 10.1007/s00401-014-1365-0
999 C 5 |9 -- missing cx lookup --
|a 10.1091/mbc.E04-11-0992
|2 Crossref
|o 10.1091/mbc.E04-11-0992
999 C 5 |9 -- missing cx lookup --
|a 10.1038/nature13787
|2 Crossref
|o 10.1038/nature13787
999 C 5 |9 -- missing cx lookup --
|a 10.1016/j.neuron.2014.07.041
|2 Crossref
|o 10.1016/j.neuron.2014.07.041
999 C 5 |9 -- missing cx lookup --
|a 10.1016/j.cub.2007.09.039
|2 Crossref
|o 10.1016/j.cub.2007.09.039
999 C 5 |9 -- missing cx lookup --
|a 10.1371/journal.pone.0105632
|2 Crossref
|o 10.1371/journal.pone.0105632
999 C 5 |y 2015
|2 Crossref
|o Z Tao 2015
999 C 5 |9 -- missing cx lookup --
|a 10.1371/journal.pone.0083450
|2 Crossref
|o 10.1371/journal.pone.0083450
999 C 5 |9 -- missing cx lookup --
|a 10.1016/S1474-4422(13)70210-2
|2 Crossref
|o 10.1016/S1474-4422(13)70210-2
999 C 5 |9 -- missing cx lookup --
|a 10.1001/jamaneurol.2013.1453
|2 Crossref
|o 10.1001/jamaneurol.2013.1453
999 C 5 |9 -- missing cx lookup --
|a 10.1080/15384101.2014.995490
|2 Crossref
|o 10.1080/15384101.2014.995490
999 C 5 |9 -- missing cx lookup --
|a 10.1016/j.neuron.2014.12.010
|2 Crossref
|o 10.1016/j.neuron.2014.12.010
999 C 5 |9 -- missing cx lookup --
|a 10.1093/brain/aws001
|2 Crossref
|o 10.1093/brain/aws001
999 C 5 |y 2014
|2 Crossref
|o M Yamakawa 2014
999 C 5 |9 -- missing cx lookup --
|a 10.1038/nn.2835
|2 Crossref
|o 10.1038/nn.2835
999 C 5 |9 -- missing cx lookup --
|a 10.1007/s00401-014-1336-5
|2 Crossref
|o 10.1007/s00401-014-1336-5
999 C 5 |9 -- missing cx lookup --
|a 10.1073/pnas.1315438110
|2 Crossref
|o 10.1073/pnas.1315438110

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21