% 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{Riemenschneider:163937,
      author       = {Riemenschneider, Henrick and Guo, Qiang and Bader, Jakob
                      and Frottin, Frédéric and Farny, Daniel and Kleinberger,
                      Gernot and Haass, Christian and Mann, Matthias and Hartl, F
                      Ulrich and Baumeister, Wolfgang and Hipp, Mark S and
                      Meissner, Felix and Fernández-Busnadiego, Rubén and
                      Edbauer, Dieter},
      title        = {{G}el-like inclusions of {C}-terminal fragments of {TDP}-43
                      sequester stalled proteasomes in neurons.},
      journal      = {EMBO reports},
      volume       = {23},
      number       = {6},
      issn         = {1469-221X},
      address      = {Hoboken, NJ [u.a.]},
      publisher    = {Wiley},
      reportid     = {DZNE-2022-00611},
      pages        = {e53890},
      year         = {2022},
      note         = {(CC BY)},
      abstract     = {Aggregation of the multifunctional RNA-binding protein
                      TDP-43 defines large subgroups of amyotrophic lateral
                      sclerosis and frontotemporal dementia and correlates with
                      neurodegeneration in both diseases. In disease,
                      characteristic C-terminal fragments of ~25 kDa ('TDP-25')
                      accumulate in cytoplasmic inclusions. Here, we analyze
                      gain-of-function mechanisms of TDP-25 combining
                      cryo-electron tomography, proteomics, and functional assays.
                      In neurons, cytoplasmic TDP-25 inclusions are amorphous, and
                      photobleaching experiments reveal gel-like biophysical
                      properties that are less dynamic than nuclear TDP-43.
                      Compared with full-length TDP-43, the TDP-25 interactome is
                      depleted of low-complexity domain proteins. TDP-25
                      inclusions are enriched in 26S proteasomes adopting
                      exclusively substrate-processing conformations, suggesting
                      that inclusions sequester proteasomes, which are largely
                      stalled and no longer undergo the cyclic conformational
                      changes required for proteolytic activity. Reporter assays
                      confirm that TDP-25 impairs proteostasis, and this
                      inhibitory function is enhanced by ALS-causing TDP-43
                      mutations. These findings support a patho-physiological
                      relevance of proteasome dysfunction in ALS/FTD.},
      keywords     = {Amyotrophic Lateral Sclerosis: genetics / Amyotrophic
                      Lateral Sclerosis: metabolism / DNA-Binding Proteins:
                      genetics / DNA-Binding Proteins: metabolism / Frontotemporal
                      Dementia: genetics / Frontotemporal Dementia: metabolism /
                      Humans / Inclusion Bodies: metabolism / Neurons: metabolism
                      / Peptide Fragments: genetics / Peptide Fragments:
                      metabolism / Proteasome Endopeptidase Complex: metabolism /
                      ALS (Other) / TDP-43 (Other) / neurodegeneration (Other) /
                      phase separation (Other) / proteasome (Other)},
      cin          = {AG Edbauer / AG Lichtenthaler / AG Herms / AG Haass},
      ddc          = {570},
      cid          = {I:(DE-2719)1110004 / I:(DE-2719)1110006 /
                      I:(DE-2719)1110001 / I:(DE-2719)1110007},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC9171420},
      pubmed       = {pmid:35438230},
      doi          = {10.15252/embr.202153890},
      url          = {https://pub.dzne.de/record/163937},
}