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@ARTICLE{Seidel:136717,
      author       = {Seidel, Diana and Krinke, Dana and Jahnke, Heinz-Georg and
                      Hirche, Anika and Kloß, Daniel and Mack, Till G. A. and
                      Striggow, Frank and Robitzki, Andrea},
      title        = {{I}nduced tauopathy in a novel 3{D}-culture model mediates
                      neurodegenerative processes: a real-time study on biochips.},
      journal      = {PLOS ONE},
      volume       = {7},
      number       = {11},
      issn         = {1932-6203},
      address      = {San Francisco, California, US},
      publisher    = {PLOS},
      reportid     = {DZNE-2020-03039},
      pages        = {e49150},
      year         = {2012},
      abstract     = {Tauopathies including Alzheimer's disease represent one of
                      the major health problems of aging population worldwide.
                      Therefore, a better understanding of tau-dependent
                      pathologies and consequently, tau-related intervention
                      strategies is highly demanded. In recent years, several
                      tau-focused therapies have been proposed with the aim to
                      stop disease progression. However, to develop efficient
                      active pharmaceutical ingredients for the broad treatment of
                      Alzheimer's disease patients, further improvements are
                      necessary for understanding the detailed neurodegenerative
                      processes as well as the mechanism and side effects of
                      potential active pharmaceutical ingredients (API) in the
                      neuronal system. In this context, there is a lack of
                      suitable complex in vitro cell culture models recapitulating
                      major aspects of taupathological degenerative processes in
                      sufficient time and reproducible manner.Herewith, we
                      describe a novel 3D SH-SY5Y cell-based, tauopathy model that
                      shows advanced characteristics of matured neurons in
                      comparison to monolayer cultures without the need of
                      artificial differentiation promoting agents. Moreover, the
                      recombinant expression of a novel highly pathologic fourfold
                      mutated human tau variant lead to a fast and emphasized
                      degeneration of neuritic processes. The neurodegenerative
                      effects could be analyzed in real time and with high
                      sensitivity using our unique microcavity array-based
                      impedance spectroscopy measurement system. We were able to
                      quantify a time- and concentration-dependent relative
                      impedance decrease when Alzheimer's disease-like tau
                      pathology was induced in the neuronal 3D cell culture model.
                      In combination with the collected optical information, the
                      degenerative processes within each 3D-culture could be
                      monitored and analyzed. More strikingly, tau-specific
                      regenerative effects caused by tau-focused active
                      pharmaceutical ingredients could be quantitatively monitored
                      by impedance spectroscopy.Bringing together our novel
                      complex 3D cell culture taupathology model and our
                      microcavity array-based impedimetric measurement system, we
                      provide a powerful tool for the label-free investigation of
                      tau-related pathology processes as well as the high content
                      analysis of potential active pharmaceutical ingredient
                      candidates.},
      keywords     = {Aging: metabolism / Aging: pathology / Alzheimer Disease:
                      metabolism / Alzheimer Disease: pathology / Culture
                      Techniques: methods / Dielectric Spectroscopy / Female /
                      Humans / Microarray Analysis / Middle Aged / Nerve
                      Degeneration: metabolism / Nerve Degeneration: pathology /
                      Neurons: metabolism / Neurons: pathology / Tauopathies:
                      metabolism / Tauopathies: pathology / tau Proteins:
                      metabolism / tau Proteins (NLM Chemicals)},
      cin          = {AG Striggow},
      ddc          = {610},
      cid          = {I:(DE-2719)5000045},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:23145103},
      pmc          = {pmc:PMC3492324},
      doi          = {10.1371/journal.pone.0049150},
      url          = {https://pub.dzne.de/record/136717},
}