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@ARTICLE{Szeg:909067,
      author       = {Szegő, Éva M and Boß, Fabian and Komnig, Daniel and
                      Gärtner, Charlott and Höfs, Lennart and Shaykhalishahi,
                      Hamed and Wördehoff, Michael M and Saridaki, Theodora and
                      Schulz, Jörg B and Hoyer, Wolfgang and Falkenburger, Björn
                      H},
      title        = {{A} β-{W}rapin {T}argeting the {N}-{T}erminus of
                      α-{S}ynuclein {M}onomers {R}educes {F}ibril-{I}nduced
                      {A}ggregation in {N}eurons.},
      journal      = {Frontiers in neuroscience},
      volume       = {15},
      issn         = {1662-453X},
      address      = {Lausanne},
      publisher    = {Frontiers Research Foundation},
      reportid     = {FZJ-2022-02985},
      pages        = {696440},
      year         = {2021},
      abstract     = {Reducing α-synuclein pathology constitutes a plausible
                      strategy against Parkinson's disease. As we recently
                      demonstrated, the β-wrapin protein AS69 binds an N-terminal
                      region in monomeric α-synuclein, interferes with fibril
                      nucleation, and reduces α-synuclein aggregation in vitro
                      and in a fruit fly model of α-synuclein toxicity. The aim
                      of this study was to investigate whether AS69 also reduces
                      α-synuclein pathology in mammalian neurons. To induce
                      α-synuclein pathology, primary mouse neurons were exposed
                      to pre-formed fibrils (PFF) of human α-synuclein. PFF were
                      also injected into the striatum of A30P-α-synuclein
                      transgenic mice. The extent of α-synuclein pathology was
                      determined by phospho-α-synuclein staining and by Triton
                      X-100 solubility. The degeneration of neuronal somata,
                      dendrites, and axon terminals was determined by
                      immunohistochemistry. AS69 and PFF were taken up by primary
                      neurons. AS69 did not alter PFF uptake, but AS69 did reduce
                      PFF-induced α-synuclein pathology. PFF injection into mouse
                      striatum led to α-synuclein pathology and dystrophic
                      neurites. Co-injection of AS69 abrogated PFF-induced
                      pathology. AS69 also reduced the PFF-induced degeneration of
                      dopaminergic axon terminals in the striatum and the
                      degeneration of dopaminergic dendrites in the substantia
                      nigra pars reticulata. AS69 reduced the activation of
                      astroglia but not microglia in response to PFF injection.
                      Collectively, AS69 reduced PFF-induced α-synuclein
                      pathology and the associated neurodegeneration in primary
                      neurons and in mouse brain. Our data therefore suggest that
                      small proteins binding the N-terminus of α-synuclein
                      monomers are promising strategies to modify disease
                      progression in Parkinson's disease.},
      keywords     = {molecular chaperones (Other) / nanobodies (Other) /
                      pre-formed fibrils (Other) / protein aggregation (Other) /
                      α-synuclein (Other)},
      cin          = {IBI-7},
      ddc          = {610},
      cid          = {I:(DE-Juel1)IBI-7-20200312},
      pnm          = {5244 - Information Processing in Neuronal Networks
                      (POF4-524) / BETACONTROL - Control of amyloid formation via
                      beta-hairpin molecular recognition features (726368)},
      pid          = {G:(DE-HGF)POF4-5244 / G:(EU-Grant)726368},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34326719},
      pmc          = {pmc:PMC8313869},
      UT           = {WOS:000878869900001},
      doi          = {10.3389/fnins.2021.696440},
      url          = {https://juser.fz-juelich.de/record/909067},
}