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@ARTICLE{Bae:140159,
      author       = {Bae, Eun-Jin and Kim, Dong-Kyu and Kim, Changyoun and
                      Mante, Michael and Adame, Anthony and Rockenstein, Edward
                      and Ulusoy, Ayse and Klinkenberg, Michael and Jeong, Ga Ram
                      and Bae, Jae Ryul and Lee, Cheolsoon and Lee, He-Jin and
                      Lee, Byung-Dae and Di Monte, Donato A and Masliah, Eliezer
                      and Lee, Seung-Jae},
      title        = {{LRRK}2 kinase regulates α-synuclein propagation via
                      {RAB}35 phosphorylation.},
      journal      = {Nature Communications},
      volume       = {9},
      number       = {1},
      issn         = {2041-1723},
      address      = {[London]},
      publisher    = {Nature Publishing Group UK},
      reportid     = {DZNE-2020-06481},
      pages        = {3465},
      year         = {2018},
      abstract     = {Propagation of α-synuclein aggregates has been suggested
                      as a contributing factor in Parkinson's disease (PD)
                      progression. However, the molecular mechanisms underlying
                      α-synuclein aggregation are not fully understood. Here, we
                      demonstrate in cell culture, nematode, and rodent models of
                      PD that leucine-rich repeat kinase 2 (LRRK2), a PD-linked
                      kinase, modulates α-synuclein propagation in a kinase
                      activity-dependent manner. The PD-linked G2019S mutation in
                      LRRK2, which increases kinase activity, enhances propagation
                      efficiency. Furthermore, we show that the role of LRRK2 in
                      α-synuclein propagation is mediated by RAB35
                      phosphorylation. Constitutive activation of RAB35 overrides
                      the reduced α-synuclein propagation phenotype in lrk-1
                      mutant C. elegans. Finally, in a mouse model of
                      synucleinopathy, administration of an LRRK2 kinase inhibitor
                      reduced α-synuclein aggregation via enhanced interaction of
                      α-synuclein with the lysosomal degradation pathway. These
                      results suggest that LRRK2-mediated RAB35 phosphorylation is
                      a potential therapeutic target for modifying disease
                      progression.},
      keywords     = {Animals / Blotting, Western / Caenorhabditis elegans:
                      genetics / Caenorhabditis elegans: metabolism /
                      Caenorhabditis elegans Proteins: genetics / Caenorhabditis
                      elegans Proteins: metabolism / Cell Line, Tumor / Humans /
                      Leucine-Rich Repeat Serine-Threonine Protein Kinase-2:
                      genetics / Leucine-Rich Repeat Serine-Threonine Protein
                      Kinase-2: metabolism / Microscopy, Fluorescence /
                      Phosphorylation / Plasmids: genetics / Rats /
                      alpha-Synuclein: genetics / alpha-Synuclein: metabolism /
                      rab GTP-Binding Proteins: genetics / rab GTP-Binding
                      Proteins: metabolism / Caenorhabditis elegans Proteins (NLM
                      Chemicals) / Rab-35 protein, C elegans (NLM Chemicals) /
                      alpha-Synuclein (NLM Chemicals) / Leucine-Rich Repeat
                      Serine-Threonine Protein Kinase-2 (NLM Chemicals) / rab
                      GTP-Binding Proteins (NLM Chemicals)},
      cin          = {AG Di Monte},
      ddc          = {500},
      cid          = {I:(DE-2719)1013008},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30150626},
      pmc          = {pmc:PMC6110743},
      doi          = {10.1038/s41467-018-05958-z},
      url          = {https://pub.dzne.de/record/140159},
}