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@ARTICLE{Bopp:282913,
      author       = {Bopp, Verena and Lee, Jaehyun and Oeckl, Patrick and
                      Kühlwein, Julia and Grozdanov, Veselin and Kiechle, Martin
                      and Mayer, Benjamin and Möhrle, Bettina and Geiger, Hartmut
                      and Danzer, Karin M.},
      title        = {{T}argeting {C}dc42 improves motor phenotype in
                      {P}arkinson’s disease mice and reveals age-dependent
                      susceptibility to α-synuclein},
      journal      = {iScience},
      volume       = {28},
      number       = {12},
      issn         = {2589-0042},
      address      = {St. Louis},
      publisher    = {Elsevier},
      reportid     = {DZNE-2025-01374},
      pages        = {114217},
      year         = {2025},
      abstract     = {Aging and accumulation of α-synuclein (α-syn) oligomers
                      in the brain are indisputably linked to Parkinson’s
                      disease (PD). Using an inducible α-syn oligomer mouse
                      model, we demonstrate that the induction of PD-associated
                      α-syn oligomers for the same time span caused PD-associated
                      symptoms only in aged, but not in young mice. Biochemical
                      studies revealed that α-syn oligomer formation precedes
                      motor decline, with age and α-syn expression jointly
                      determining the motor phenotype. Single-nucleus RNA
                      sequencing (snRNA-seq) identified a PD-related
                      transcriptional signature in basal ganglia neurons (BGNs),
                      which overlapped in part with aging-associated changes.
                      Short-term pharmacological inhibition of the small RhoGTPase
                      CDC42 in aged, symptomatic animals improved motor function
                      without reducing oligomer levels. These findings indicate
                      that aging processes strongly influence the susceptibility
                      to PD-like symptoms and that targeting age-related pathways,
                      rather than α-syn oligomer burden alone, may provide
                      effective strategies to improve outcomes in PD.},
      cin          = {AG Danzer / AG Öckl},
      ddc          = {050},
      cid          = {I:(DE-2719)5000072 / I:(DE-2719)5000073},
      pnm          = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
                      Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1016/j.isci.2025.114217},
      url          = {https://pub.dzne.de/record/282913},
}