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@ARTICLE{Saidi:137778,
      author       = {Saidi, Laiq-Jan and Polydoro, Manuela and Kay, Kevin R and
                      Sanchez, Laura and Mandelkow, Eva-Maria and Hyman, Bradley T
                      and Spires-Jones, Tara L},
      title        = {{C}arboxy terminus heat shock protein 70 interacting
                      protein reduces tau-associated degenerative changes.},
      journal      = {Journal of Alzheimer's disease},
      volume       = {44},
      number       = {3},
      issn         = {1875-8908},
      address      = {Amsterdam},
      publisher    = {IOS Press},
      reportid     = {DZNE-2020-04100},
      pages        = {937-947},
      year         = {2015},
      abstract     = {One of the hallmarks of Alzheimer's disease is the
                      formation of neurofibrillary tangles, intracellular
                      aggregates of hyperphosphorylated, mislocalized tau protein,
                      which are associated with neuronal loss. Changes in tau are
                      known to impair cellular transport (including that of
                      mitochondria) and are associated with cell death in cell
                      culture and mouse models of tauopathy. Thus clearing
                      pathological forms of tau from cells is a key therapeutic
                      strategy. One critical modulator in the degradation and
                      clearance of misfolded proteins is the co-chaperone CHIP
                      (Carboxy terminus Hsp70 interacting Protein), which is known
                      to play a role in refolding and clearance of
                      hyperphosphorylated tau. Here, we tested the hypothesis that
                      CHIP could ameliorate pathological changes associated with
                      tau. We find that co-expressing CHIP with full-length tau,
                      tau truncated at D421 mimicking caspase cleavage, or the
                      short tauRDΔK280 tau construct containing only the tau
                      repeat domain with a tauopathy mutation, decreases tau
                      protein levels in human H4 neuroglioma cells in a manner
                      dependent on the Hsp70-binding TPR domain of CHIP. The
                      observed reduction in tau levels by CHIP is associated with
                      a decrease of tau phosphorylation and reduced levels of
                      cleaved Caspase 3 indicating that CHIP plays an important
                      role in preventing tau-induced pathological changes.
                      Furthermore, tau-associated mitochondrial transport deficits
                      are rescued by CHIP co-expression in H4 cells. Together,
                      these data suggest that the co-chaperone CHIP can rescue the
                      pathological effects of tau, and indicate that other
                      diseases of protein misfolding and accumulation may also
                      benefit from CHIP upregulation.},
      keywords     = {Caspase 3: pharmacology / Cell Line, Tumor / Cell
                      Proliferation: genetics / Gene Expression Regulation: drug
                      effects / Gene Expression Regulation: genetics / Green
                      Fluorescent Proteins: genetics / Green Fluorescent Proteins:
                      metabolism / HSP70 Heat-Shock Proteins: genetics / HSP70
                      Heat-Shock Proteins: metabolism / Humans / Mitochondria:
                      metabolism / Mutation: genetics / Neuroblastoma: pathology /
                      Protein Binding: drug effects / Transfection /
                      Ubiquitin-Protein Ligases: genetics / Ubiquitin-Protein
                      Ligases: metabolism / tau Proteins: genetics / tau Proteins:
                      metabolism / HSP70 Heat-Shock Proteins (NLM Chemicals) / tau
                      Proteins (NLM Chemicals) / Green Fluorescent Proteins (NLM
                      Chemicals) / STUB1 protein, human (NLM Chemicals) /
                      Ubiquitin-Protein Ligases (NLM Chemicals) / Caspase 3 (NLM
                      Chemicals)},
      cin          = {AG Mandelkow 2},
      ddc          = {610},
      cid          = {I:(DE-2719)1013015},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:25374103},
      doi          = {10.3233/JAD-142094},
      url          = {https://pub.dzne.de/record/137778},
}