% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Mori:137126,
      author       = {Mori, Kohji and Arzberger, Thomas and Grässer, Friedrich A
                      and Gijselinck, Ilse and May, Stephanie and Rentzsch,
                      Kristin and Weng, Shih-Ming and Schludi, Martin H and van
                      der Zee, Julie and Cruts, Marc and Van Broeckhoven,
                      Christine and Kremmer, Elisabeth and Kretzschmar, Hans A and
                      Haass, Christian and Edbauer, Dieter},
      title        = {{B}idirectional transcripts of the expanded {C}9orf72
                      hexanucleotide repeat are translated into aggregating
                      dipeptide repeat proteins.},
      journal      = {Acta neuropathologica},
      volume       = {126},
      number       = {6},
      issn         = {0001-6322},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DZNE-2020-03448},
      pages        = {881-893},
      year         = {2013},
      abstract     = {Massive 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.},
      keywords     = {Amyotrophic Lateral Sclerosis: diagnosis / Amyotrophic
                      Lateral Sclerosis: genetics / Amyotrophic Lateral Sclerosis:
                      metabolism / Brain: metabolism / C9orf72 Protein / DNA
                      Repeat Expansion / Frontotemporal Lobar Degeneration:
                      diagnosis / Frontotemporal Lobar Degeneration: genetics /
                      Frontotemporal Lobar Degeneration: metabolism / Humans /
                      Protein Biosynthesis / Proteins: genetics / Proteins:
                      metabolism / C9orf72 Protein (NLM Chemicals) / C9orf72
                      protein, human (NLM Chemicals) / Proteins (NLM Chemicals)},
      cin          = {AG Levin / AG Edbauer / Ext HZM / AG Haass},
      ddc          = {610},
      cid          = {I:(DE-2719)1111016 / I:(DE-2719)1110004 /
                      I:(DE-2719)5000050 / I:(DE-2719)1110007},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342) / 344
                      - Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-342 / G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:24132570},
      doi          = {10.1007/s00401-013-1189-3},
      url          = {https://pub.dzne.de/record/137126},
}