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000137126 0247_ $$2doi$$a10.1007/s00401-013-1189-3
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000137126 037__ $$aDZNE-2020-03448
000137126 041__ $$aEnglish
000137126 082__ $$a610
000137126 1001_ $$aMori, Kohji$$b0
000137126 245__ $$aBidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins.
000137126 260__ $$aHeidelberg$$bSpringer$$c2013
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000137126 520__ $$aMassive GGGGCC repeat expansion in the first intron of the gene C9orf72 is the most common known cause of familial frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Despite its intronic localization and lack of an ATG start codon, the repeat region is translated in all three reading frames into aggregating dipeptide-repeat (DPR) proteins, poly-(Gly-Ala), poly-(Gly-Pro) and poly-(Gly-Arg). We took an antibody-based approach to further validate the translation of DPR proteins. To test whether the antisense repeat RNA transcript is also translated, we raised antibodies against the predicted products, poly-(Ala-Pro) and poly-(Pro-Arg). Both antibodies stained p62-positive neuronal cytoplasmic inclusions throughout the cerebellum and hippocampus indicating that not only sense but also antisense strand repeats are translated into DPR proteins in the absence of ATG start codons. Protein products of both strands co-aggregate suggesting concurrent translation of both strands. Moreover, an antibody targeting the putative carboxyl terminus of DPR proteins can detect inclusion pathology in C9orf72 repeat expansion carriers suggesting that the non-ATG translation continues through the entire repeat and beyond. A highly sensitive monoclonal antibody against poly-(Gly-Arg), visualized abundant inclusion pathology in all cortical regions and some inclusions also in motoneurons. Together, our data show that the GGGGCC repeat is bidirectionally translated into five distinct DPR proteins that co-aggregate in the characteristic p62-positive TDP-43 negative inclusions found in FTLD/ALS cases with C9orf72 repeat expansion. Novel monoclonal antibodies against poly-(Gly-Arg) will facilitate pathological diagnosis of C9orf72 FTLD/ALS.
000137126 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
000137126 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x1
000137126 542__ $$2Crossref$$i2013-10-17$$uhttp://www.springer.com/tdm
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000137126 650_7 $$2NLM Chemicals$$aC9orf72 Protein
000137126 650_7 $$2NLM Chemicals$$aC9orf72 protein, human
000137126 650_7 $$2NLM Chemicals$$aProteins
000137126 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: diagnosis
000137126 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: genetics
000137126 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: metabolism
000137126 650_2 $$2MeSH$$aBrain: metabolism
000137126 650_2 $$2MeSH$$aC9orf72 Protein
000137126 650_2 $$2MeSH$$aDNA Repeat Expansion
000137126 650_2 $$2MeSH$$aFrontotemporal Lobar Degeneration: diagnosis
000137126 650_2 $$2MeSH$$aFrontotemporal Lobar Degeneration: genetics
000137126 650_2 $$2MeSH$$aFrontotemporal Lobar Degeneration: metabolism
000137126 650_2 $$2MeSH$$aHumans
000137126 650_2 $$2MeSH$$aProtein Biosynthesis
000137126 650_2 $$2MeSH$$aProteins: genetics
000137126 650_2 $$2MeSH$$aProteins: metabolism
000137126 7001_ $$0P:(DE-2719)2811333$$aArzberger, Thomas$$b1$$udzne
000137126 7001_ $$aGrässer, Friedrich A$$b2
000137126 7001_ $$aGijselinck, Ilse$$b3
000137126 7001_ $$0P:(DE-2719)2762699$$aMay, Stephanie$$b4$$udzne
000137126 7001_ $$0P:(DE-2719)2501892$$aRentzsch, Kristin$$b5$$udzne
000137126 7001_ $$0P:(DE-2719)9000401$$aWeng, Shih-Ming$$b6$$udzne
000137126 7001_ $$0P:(DE-2719)2810746$$aSchludi, Martin H$$b7$$udzne
000137126 7001_ $$avan der Zee, Julie$$b8
000137126 7001_ $$aCruts, Marc$$b9
000137126 7001_ $$aVan Broeckhoven, Christine$$b10
000137126 7001_ $$0P:(DE-2719)9000167$$aKremmer, Elisabeth$$b11$$udzne
000137126 7001_ $$0P:(DE-HGF)0$$aKretzschmar, Hans A$$b12
000137126 7001_ $$0P:(DE-2719)2202037$$aHaass, Christian$$b13$$eCorresponding author$$udzne
000137126 7001_ $$0P:(DE-2719)2231621$$aEdbauer, Dieter$$b14$$eLast author$$udzne
000137126 77318 $$2Crossref$$3journal-article$$a10.1007/s00401-013-1189-3$$b : Springer Science and Business Media LLC, 2013-10-17$$n6$$p881-893$$tActa Neuropathologica$$v126$$x0001-6322$$y2013
000137126 773__ $$0PERI:(DE-600)1458410-4$$a10.1007/s00401-013-1189-3$$gVol. 126, no. 6, p. 881 - 893$$n6$$p881-893$$q126:6<881 - 893$$tActa neuropathologica$$v126$$x0001-6322$$y2013
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000137126 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.ajhg.2013.01.011$$o10.1016/j.ajhg.2013.01.011
000137126 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/j.1440-1789.2012.01332.x$$o10.1111/j.1440-1789.2012.01332.x
000137126 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1136/jnnp.2009.204081$$o10.1136/jnnp.2009.204081
000137126 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.tins.2013.04.010$$o10.1016/j.tins.2013.04.010
000137126 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neuron.2011.09.011$$o10.1016/j.neuron.2011.09.011
000137126 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.cell.2012.02.022$$o10.1016/j.cell.2012.02.022
000137126 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00401-013-1147-0$$o10.1007/s00401-013-1147-0
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000137126 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00401-013-1088-7$$o10.1007/s00401-013-1088-7
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000137126 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00401-008-0477-9$$o10.1007/s00401-008-0477-9
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000137126 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/j.1440-1789.2009.01043.x$$o10.1111/j.1440-1789.2009.01043.x
000137126 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nrneurol.2012.117$$o10.1038/nrneurol.2012.117
000137126 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neuron.2011.09.010$$o10.1016/j.neuron.2011.09.010
000137126 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neuron.2013.03.026$$o10.1016/j.neuron.2013.03.026
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000137126 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.ajhg.2013.04.017$$o10.1016/j.ajhg.2013.04.017
000137126 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.2353/ajpath.2007.060576$$o10.2353/ajpath.2007.060576
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