% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Messing:136827,
      author       = {Messing, Lars and Decker, Jochen Martin and Joseph, Maria
                      and Mandelkow, Eckhard and Mandelkow, Eva-Maria},
      title        = {{C}ascade of tau toxicity in inducible hippocampal brain
                      slices and prevention by aggregation inhibitors.},
      journal      = {Neurobiology of aging},
      volume       = {34},
      number       = {5},
      issn         = {0197-4580},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DZNE-2020-03149},
      pages        = {1343-1354},
      year         = {2013},
      abstract     = {Mislocalization and aggregation of the axonal protein tau
                      are hallmarks of Alzheimer's disease and other tauopathies.
                      Here, we studied the relationship between tau aggregation,
                      loss of spines and neurons, and reversibility by aggregation
                      inhibitors. To this end we established an in vitro model of
                      tauopathy based on regulatable transgenic hippocampal
                      organotypic slice cultures prepared from mice expressing
                      proaggregant Tau repeat domain with mutation ΔK280
                      (Tau(RD)ΔK). Transgene expression was monitored by a
                      bioluminescence reporter assay. We observed abnormal tau
                      phosphorylation and mislocalization of exogenous and
                      endogenous tau into the somatodendritic compartment. This
                      was paralleled by a reduction of dendritic spines, altered
                      dendritic spine morphology, dysregulation of Ca(++) dynamics
                      and elevated activation of microglia. Neurotoxicity was
                      mediated by Caspase-3 activation and correlated with the
                      expression level of proaggregant Tau(RD)ΔK. Finally, tau
                      aggregates appeared in areas CA1 and CA3 after three weeks
                      in vitro. Neurodegeneration was relieved by aggregation
                      inhibitors or by switching off transgene expression. Thus
                      the slice culture model is suitable for monitoring the
                      development of tauopathy and the therapeutic benefit of
                      antiaggregation drugs.},
      keywords     = {Animals / Calcium Signaling / Cells, Cultured /
                      Dimerization / Hippocampus: pathology / Hippocampus:
                      physiopathology / Mice / Mice, Transgenic / Neurons:
                      pathology / Tauopathies: physiopathology / tau Proteins:
                      metabolism / Mapt protein, mouse (NLM Chemicals) / tau
                      Proteins (NLM Chemicals)},
      cin          = {Tech Transfer / AG Mandelkow 2 / AG Mandelkow 1},
      ddc          = {610},
      cid          = {I:(DE-2719)1030028 / I:(DE-2719)1013015 /
                      I:(DE-2719)1013014},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:23158765},
      pmc          = {pmc:PMC4984976},
      doi          = {10.1016/j.neurobiolaging.2012.10.024},
      url          = {https://pub.dzne.de/record/136827},
}