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@ARTICLE{Tittelmeier:186273,
      author       = {J. Tittelmeier and S. Druffel-Augustin and A. Alik and R.
                      Melki and C. Nussbaum-Krammer$^*$},
      title        = {{D}issecting aggregation and seeding dynamics of α-{S}yn
                      polymorphs using the phasor approach to {FLIM}.},
      journal      = {Communications biology},
      volume       = {5},
      number       = {1},
      issn         = {2399-3642},
      address      = {London},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2022-03062},
      pages        = {1345},
      year         = {2022},
      note         = {DKFZ-ZMBH Alliance / #LA:A250#},
      abstract     = {Synucleinopathies are a heterogenous group of
                      neurodegenerative diseases characterized by the progressive
                      accumulation of pathological α-synuclein (α-Syn). The
                      importance of structural polymorphism of α-Syn assemblies
                      for distinct synucleinopathies and their progression is
                      increasingly recognized. However, the underlying mechanisms
                      are poorly understood. Here we use fluorescence lifetime
                      imaging microscopy (FLIM) to investigate seeded aggregation
                      of α-Syn in a biosensor cell line. We show that
                      conformationally distinct α-Syn polymorphs exhibit
                      characteristic fluorescence lifetimes. FLIM further revealed
                      that α-Syn polymorphs were differentially processed by
                      cellular clearance pathways, yielding fibrillar species with
                      increased seeding capacity. Thus, FLIM is not only a
                      powerful tool to distinguish different amyloid structures,
                      but also to monitor the dynamic process of amyloid
                      remodeling by the cellular environment. Our data suggest
                      that the accumulation of highly seeding competent
                      degradation products for particular polymorphs may account
                      for accelerated disease progression in some patients.},
      keywords     = {Humans / alpha-Synuclein: genetics / Social Group /
                      alpha-Synuclein (NLM Chemicals)},
      cin          = {A250},
      ddc          = {570},
      cid          = {I:(DE-He78)A250-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36477485},
      pmc          = {pmc:PMC9729209},
      doi          = {10.1038/s42003-022-04289-6},
      url          = {https://inrepo02.dkfz.de/record/186273},
}